会管理不良事件报告吗？来看看你是不是一个合格的监查员CRA

 探讨研究启动前、试验实施阶段和试验结束后AE报告和治疗。

安全性考虑贯彻药物临床试验设计、实施、分析和报告全程，药物进入人体前考虑药物安全性，研究整个流程和操作对人体安全性影响，和研究结束后的潜在安全性影响。

1.1: Adverse Drug Reaction (ADR) definition.

•  1.2: Adverse Event (AE) definition.

•  1.50: Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)

definition.

•  1.60: Unexpected Adverse Drug Reaction definition.

•  3.38 (c): Requirement for the investigator to report specific ADRs to the IRB.

•  4.3.2: Responsibility of the investigator to ensure care for subjects with AEs.

•  4.7: Unblinding procedures involving SAEs.

•  4.11: Investigator responsibility for safety reporting.

•  5.16: Sponsor responsibility for evaluating and reporting safety information.

•  5.17: Sponsor responsibility for reporting adverse drug reactions.

•  8.3.17: Filing of documents about unexpected adverse drug reactions and other safety

information.

 ICH E6对AE定义如下，Adverse Event (AE)：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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product.

 结合前部分介绍，从以上定义可看出，AE包括研究期间新出现或比基线期恶化的疾病、损伤、体征和症状，也包括。AE出现不需要和药物一定存在因果关系，凡研究期间（或方案规定的其它时间窗，很多外企都将AE收集日期定义在ICF签署日期起，便于评估用药后AE前后对比）发生过就被包括在内。

如体征和症状提示具体状况（疾病或损伤），AE报告该状况。反之，体征和症状本身报告AE。因而“恶心和呕吐”应作为两个事件报告，如1恶心，2呕吐。手术治疗并非AE，而引起手术或相关治疗干预的医学状况是AE。

Adverse Drug Reaction (ADR). In a preapproval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established, all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase “responses to a medicinal product” means that a causal relationship between the medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out。

         ADR是研究药物引起的AE，关联性判定取决于研究者。

 Unexpected Adverse Drug Reaction. An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g.,Investigator’s Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product)。

非预期不良药物反应是判定与使用IP有关且IB或标签并未描述该AE为IP的副作用。无IB相关信息时，判定AE是否非预期基于描述在总体药物计划中的风险信息。 

        Serious Adverse Event (SAE). Any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

上述关于SAE原则同样适用于AE，例如AE不管是否和使用IP有关，仅需要确认发生在研究过程中或方案特定的时间框架内，其它重要的SAE定义我们逐一简要讨论：

       Disability. A substantial disruption of a person’s ability to conduct normal life functions。

   例子如，视觉丧失，无行动能力，行动不便，或丧失认知能力。

Life-threatening. Places the subject, in the view of the investigator, at immediate risk of death as it occurs; it does not include an experience that, had it occurred in a more severe form, might have caused death。

指发生需要立即采取措施应对紧急死亡威胁的事件。

Serious adverse drug experience. Any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect。

严重不良药物反应/体验，是研究者判定为与使用研究药物相关联的SAE。研究者是对受试者死亡威胁的负责人（尽管法规或有模糊之处），因而需对严重性和不良事件诱因分类并报告给申办方。