第1个回答 2022-07-14
Part 5: Adverse Event Follow-up
Part 6: Summary of Key Points
Unless otherwise specified in the protocol, in some networks it is common practice that all AEs and non- study–related SAEs should be followed-up until they have resolved or stabilized or until 30 days after the participant’s involvement in the study has ended, whichever occurs sooner.
除非协议中另有规定，在一些网络中，通常的做法是 对所有不良事件和非研究相关的严重不良事件进行随访，直到它们得到解决或稳定，或者直到参与者参与研究结束后30天，以较早发生者为准。
All SAEs should be followed until resolution, or until the condition has stabilized with no further change expected. According to FDA guidance, participants should receive appropriate medical evaluation and treatment until resolution of any emergent condition related to the study intervention that develops during or after the course of their participation in a study, even if the follow-up period extends beyond the end of the study.
应遵循所有SAE，直到问题得到解决，或直到情况稳定且预计不会发生进一步变化。根 据FDA的指导，参与者应接受适当的医疗评估和治疗，直到其参与研究期间或之后出现的与研究干预相关的任何紧急情况得到解决， 即使随访期延长到研究结束之后。
When a participant discontinues participation in a study because of an SAE, investigators should:
当参与者因为SAE而停止参与某项研究时，研究人员应：
Ⅰ、Continue to follow up the SAE as noted above.
Ⅱ、Document the SAE and its follow-up in the participant’s record.
Ⅲ、Attempt to complete any final evaluations required by the study protocol.
Ⅳ、Attempt to perform other medical evaluations to try to determine the cause of the SAE and its possible relationship to the study intervention. These evaluations would include obtaining an autopsy report, if available, in the event of a participant’s death.
1、继续 跟进上述SAE 。
2、在参与者记录中 记录SAE及其后续行动 。
3、尝试完成研究方案要求的任何 最终评估 。
4、尝试进行其他医学评估，以确定SAE的原因及其与研究干预的可能关系。这些评估包括在参与者死亡的情况下获得尸检报告（如有）。
For a woman who is discontinued from a study because of pregnancy, attempt to follow up the outcome of the pregnancy to term. If the woman was enrolled in a trial of an investigational drug that is known to present a risk of birth defects, any information regarding birth or congenital abnormality should be obtained.
对于因怀孕而中止研究的女性，尝试跟踪妊娠至足月的结果。如果该妇女 参加了已知存在出生缺陷风险的试验药物的试验，则应获得有关出生或先天异常的任何信息 。
Loss to follow-up of participants with ongoing SAEs is a serious problem that can affect the validity of a study’s results. For this reason, every effort should be made to contact participants who leave a study after experiencing an SAE. Documentation of that effort should be maintained by the PI.
对患有持续严重不良事件的受试者的随访失败是一个严重的问题 ，可能会影响研究结果的有效性。因此，应尽一切努力联系经历SAE后离开研究的参与者。PI应保存该工作的文件。
Data and safety monitoring plays an essential role in protecting participant safety and ensuring the integrity of a research study. The objectives of data and safety monitoring are to:
数据和安全监控在保护参与者安全和确保研究完整性方面起着至关重要的作用 。数据和安全监控的目标是：
Ⅰ、Ensure that risks of participation in a clinical study are minimized as far as is reasonably possible.
Ⅱ、Avoid exposing participants to excessive risk.
Ⅲ、Ensure the integrity of the data collected in a clinical study.
Ⅳ、Stop a study
i、If safety concerns arise, or
ii、As soon as the study objectives have been overwhelmingly met, criteria usually spelled out before the study begins.
1、确保尽可能降低参与临床研究的风险。
2、避免参与者面临过度风险。
3、确保临床研究中收集的数据的完整性。
4、停止学习
（1）如果出现安全问题，或
（2）一旦完全达到研究目标，通常在研究开始前制定标准。
The following are key points to remember about data and safety monitoring:
以下是有关数据和安全监控的要点：
Ⅰ、Data and safety monitoring must occur periodically throughout every study. The frequency of monitoring is commensurate with the risks involved in the study, as well as the size and complexity of the study (i.e. a small, single-site Phase I trial versus a large, blinded, multi-site Phase III trial).
1、在每次研究过程中，必须定期进行数据和安全监测。 监测频率与研究中涉及的风险以及研究的规模和复杂性 （即小型、单点i期试验与大型、盲法、多点III期试验）相称
Ⅱ、Periodic data summary reports are prepared to determine if the study should change in any way or stop. Any significant changes in the study are implemented with the approval of the local IRB and reported to appropriate institutional officials, the study sponsor, and the FDA (if the study involves an investigational new drug or device).
2、准备定期数据总结报告，以确定研究是否应以任何方式改变或停止。 本研究中的任何重大变化均应在获得当地IRB批准后实施，并向相关机构官员、研究赞助者和FDA报告 （如果本研究涉及研究新药或装置）。
Ⅲ、The risks and benefits of the study must be reassessed whenever any new study data become available.
3、一旦有了新的研究数据，就必须 重新评估这项研究的风险和益处 。
Scenario : Based on the research protocol for a behavioral non-drug study, research staff report all serious adverse events (SAEs) and report adverse events (AEs) only when an increase in the severity or frequency of a pre-existing symptom or condition occurs.
情景 ：根据行为非药物研究的研究方案，研究人员报告所有严重不良事件（SAE），并且仅当先前存在的症状或条件的严重程度或频率增加时才报告不良事件（AE）。
Question : For participants that were screened, enrolled, and randomized sometime prior to experiencing the medical events described below, which are considered SAEs?
问题 ：对于在经历以下所述医疗事件之前经过筛选、登记和随机分组的参与者，哪些被视为严重不良事件？
A. Participant reports severe neck pain after a whiplash injury in a car accident that occurred in the previous week.
B. Participant reports an ER visit due to pneumonia and was hospitalized subsequently for treatment with intravenous antibiotics.
C. Participant with a history of mild asthma reports a 2-day hospital stay for severe asthma attack treatment in the study’s final week.
D. Participant (A) and (B) only
E. Participant (B) and (C) only
F. Participant (A) and (C) only
1、参与者报告在前一周发生的车祸中颈部扭伤后出现严重颈部疼痛。
2、参与者报告因肺炎就诊，随后住院接受静脉抗生素治疗。
3、有轻度哮喘病史的参与者报告在研究的最后一周因严重哮喘发作而住院2天。
4、仅限参与者（A）和（B）
5、仅限参与者（B）和（C）
6、仅限参与者（A）和（C）
Feedback : Which is the best response: A, B, C, D, E, or F? For Scenario B, the participant experienced a medical occurrence that led to hospitalization. For Scenario C, the participant’s pre-existing condition worsened to require intensive treatment and a hospital stay. Both cases are considered SAEs. Therefore, the correct response is E.
反馈 ：A、B、C、D、E或F哪个是最好的回答？对于方案B，参与者经历了导致住院的医疗事故。对于情景C，参与者先前存在的病情恶化，需要强化治疗和住院。这两种情况都被视为严重不良事件。因此，正确的回答是E。
Question : A 15 year old male has come in for a site visit. The participant was randomized to product Z for treatment of severe cystic acne. The participant’s parents report that after several weeks on the treatment the participant had mood swings, was crying, said he was “feeling blue” and attempted suicide. The participant discontinued the drug.
问题：一名15岁的男性来现场参观。参与者被随机分配到产品Z治疗严重囊性痤疮。受试者的父母报告说，接受治疗数周后，受试者情绪波动，哭泣，说他“感到忧郁”，并试图自杀。受试者停药。
Is this a reportable event(s)?
A. Yes
B. No
Feedback: Which is the best response: A or B? Suicide attempt is a reportable event. Therefore, the correct response is A.
反馈：哪一个是最好的回答：A还是B？自杀未遂是应报告的事件。因此，正确的回答是A。
Ⅰ、The safety and well-being of study participants must be safeguarded at all times during the conduct of a clinical research study.
1、在进行临床研究期间，必须始终保障研究参与者的安全和福祉。
Ⅱ、An adverse event (AE) is defined in the Good Clinical Practice guidelines as any “untoward medical occurrence” in a person who receives a drug while participating in a clinical study. The occurrence need not be causally related to the drug treatment.
2、不良事件（AE）在《良好临床实践指南》中定义为 在参与临床研究期间服用药物的人的任何“不良医疗事件” 。这种情况的发生 不一定与药物治疗有因果关系 。
Ⅲ、For behavioral studies, 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.”
3、对于行为研究，AE可定义为 “研究过程中出现的任何不利、意外的诊断、症状、体征（包括异常的实验室发现）、综合征或疾病，在基线检查时未出现，或者在基线检查时出现，则会恶化。 ”
Ⅳ、An AE is considered serious if it poses a threat to the patient’s life or functioning. The U.S. Food and Drug Administration (FDA) defines a serious adverse event (SAE) as any untoward medical occurrence that:
i、Results in death, or
ii、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 congenital anomaly/birth defect, or
vi、Requires medical intervention to prevent one of the above outcomes.
4、如果AE对患者的生命或功能构成威胁，则视为严重AE。美国食品和药物管理局（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） 是先天性异常/出生缺陷 ，或
（6）需要 医疗干预 以防止上述结果之一。
Ⅴ、The Investigator in a behavioral trial may modify or expand the FDA criteria for an SAE to reflect the specific risks of the intervention and the characteristics of the study population.
5、行为试验中的研究者可修改或扩展FDA SAE标准，以反映干预的具体风险和研究人群的特征。
Ⅵ、The severity of an AE is not the same as its seriousness. An adverse event may be severe (e.g., severe pain from a toothache) without being serious (threatening the patient’s life or functioning).
6、不 良事件的严重程度与其严重程度不同 。不良事件可能是严重的（如牙痛引起的剧烈疼痛），但并不严重（威胁患者的生命或功能）。
Ⅶ、SAEs must be reported by phone or fax immediately to all parties notified as specified in the protocol.
7、严重不良事件必须立即通过电话或传真报告给协议中规定的所有相关方。
Ⅷ、The purpose of expedited reporting to the FDA or other regulatory authority is to ensure that the appropriate parties—including investigators, sponsors, regulators, and IRBs—are quickly made aware of new, important information about the potential adverse effects of a drug or other experimental intervention.
8、向FDA或其他监管机构快速报告的目的是 确保相关方 （包括调查人员、赞助者、监管机构和IRB） 迅速了解有关药物或其他实验干预潜在不良反应的新的重要信息 。
Ⅸ、In addition to reporting AEs and SAEs, NIH-funded studies are required to report unanticipated problems that affect the safety of study participants and others. While unanticipated problems are found in and regulated by 45 CFR 46, OHRP provides the criteria for determining unanticipated problems and the reporting and review of these incidents (see OHRP, 2007).
9、除了报告不良事件和严重不良事件外， NIH资助的研究还需要报告影响研究参与者和其他人安全的意外问题。 虽然《美国联邦法规汇编》第45卷第46节中发现并规定了意外问题，但OHRP提供了确定意外问题以及报告和审查这些事件的标准（见OHRP，2007）。
Ⅹ、Generally, all AEs and SAEs should be followed up until they have resolved or stabilized.
10、一般来说，所有的AEs和SAEs都应该被跟踪，直到它们被解决或稳定下来。
Ⅺ、Data and safety monitoring must occur periodically throughout every study to protect participant safety and ensure the integrity of study data, for example, by the Data and Safety Monitoring Board for a clinical trial.
11、 数据和安全性监测必须在每项研究中定期进行 ， 以保护参与者的安全性并确保研究数据的完整性 ，例如，由临床试验数据和安全性监测委员会进行监测。