不良事件收集：一个事件或多个事件
健康
健康医疗
2024-09-24 17:19
内蒙古
不良事件收集：一个事件或多个事件
Adverse Event Collection: one event or multiple events
2018年04月30日
April 30, 2018
在不良事件发生过程中出现严重程度变化或严重性变化的情况下，如何在数据库中记录不良事件，是我们经常遇到的问题。We constantly run into the issue how to record the adverse event in the database in the situation there is a severity change or seriousness change during the course of the adverse event.1) 临床试验中的一名受试者报告有轻度头痛。两天后，头痛的程度变为中度。然后，头痛的程度又变为轻度。在这种情况下，我们是将其记录为一个中度的头痛事件，还是记录为三个头痛事件（只要严重程度发生变化，就记录一个新的事件）? 1) A subject in clinical trial reported a mild headache. Two days later, the headache became moderate in severity. Then headache became mild in severity again.In this case, shall we record this as one headache event with moderate severity or record as three headache events (a new event is record whenever there is a severity change)?2) 同理，临床试验中的一名受试者报告了一个非严重不良事件。几天后，受试者需要住院治疗这个不良事件——现在该事件符合严重性标准。在非严重不良事件变得严重的情况下，我们是将其记录为一个注明严重程度的AE，还是将其分别记录为两个AE(一个非SAE和一个SAE)?2) Similarly, a subject in clinical trial reported a non-serious adverse event. Several days later, subject needs to be hospitalized for this adverse event – now the event meets the seriousness criteria.In a situation of a non-serious adverse event becoming serious, shall we record it as a single AE with seriousness or shall we record as two separate AEs (one non-serious AE and one serious AE)?鉴于您简短的描述，受试者的头痛仍在持续，似乎最好将此不良事件报告为严重程度可变的单一事件。然而，主要研究者的临床判断(或者，如果主要研究者不是临床医师，则是研究的医师顾问)将有助于明确症状，从而报告不良事件。相比于您提供的情形，常有一些临床情景，需要更多信息进一步了解。例如，受试者的症状可以表现为连续几天的持续头痛，或时间有限且强度不同的间歇性头痛，或另一个事件（如血压变化）的某个症状。住院事件也是如此。Given your brief description that the subject's headache is ongoing, it would seem that this adverse event would best be reported as a single event with variable severity. However, the clinical judgment of the principal investigator (or, if the principal investigator is not a clinician, then a physician consultant to the research) would be helpful in clarifying the symptoms and hence the reporting of the adverse event(s). There are several cogent clinical scenarios the understanding of which would require more information than you have supplied. For example, the subject's symptomatology could represent an unremitting headache of several days duration or episodic headaches of finite duration with varying intensities or a symptom of another event altogether such as a change in blood pressure, etc. The same would apply for the hospitalization event.为了最好地分类不良事件，并进行适当的报告，我建议对头痛进行临床评估。此外，方案可能会详细说明如何报告不良事件。同时，申办者（我不确定在这个试验中[Redacted]的状态，也就是说：是/不是申办者。）可能有不良事件报告的规范说明可以指导您。如果您仍然感到不确定，我强烈建议您联系管理该试验的FDA审查部门。To best sort out the adverse event(s) itself and therefore the appropriate reporting, I would recommend a clinical assessment of the headache. In addition, the protocol may have detailed how adverse events should be reported. As well, the sponsor (I'm not sure of [Redacted] status in this trial, i.e., is/is not the sponsor) may have specifications for adverse event reporting that could guide you. If you still feel uncertain, I would strongly recommend contacting the FDA review division regulating this trial.最后，如果相同的“事件模式”重现比较明显，建议申办者明确说明不良事件报告的标准，以便在报告头痛时保持一致性。Lastly, if it becomes apparent that this same "fact pattern" recurs, it may be advisable for the sponsor to clearly articulate standards for adverse event reporting such that there can be consistency in reporting of headaches.请参阅312.32 节IND安全报告。CFR -联邦法规第21章Please see Section 312.32 IND safety reporting. CFR - Code of Federal Regulations Title 21根据FDA 312.32节的规定，疑似不良反应是指——存在药物引起不良事件的合理相关性的任何不良事件。就IND安全报告而言，“合理相关性”意味着有证据表明药物和不良事件之间存在因果关系。疑似不良反应意味着因果关系的确定性程度低于不良反应，即由药物引起的任何不良事件。In the FDA regulations under 312.32 a suspected adverse reaction means -- any adverse event for which there is a reasonable possibility that the drug caused the adverse event. For the purposes of IND safety reporting, "reasonable possibility" means there is evidence to suggest a causal relationship between the drug and the adverse event. Suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which means any adverse event caused by a drug.这个定义与AE不同。FDA法规定义了某个AE——某个不良事件或疑似不良反应被认为是“严重的”，如果研究者或申办者认为它导致以下任一结果：死亡，危及生命的不良事件，导致住院治疗或延长现有住院治疗，持续或严重丧失能力或实质性干扰正常生活功能，或先天性异常/出生缺陷。重要医学事件可能不会导致死亡，危及生命，或者需要住院治疗，基于适当的医疗判断, 当其可能被视为严重时，他们可能危及患者或受试者，可能需要医疗或手术干预，以防止发生上述定义中列出的任何结果。此类医疗事件的例子包括需要在急诊室或家中进行强化治疗的过敏性支气管痉挛、血液恶液质或惊厥，这些并不会导致住院治疗、或发展为药物依赖或药物滥用。This definition is different than an AE. FDA regulations in defines an AE as - An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: Death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.根据FDA的规定，研究者需要向申办者报告严重不良事件，且必须包括药物导致事件是否有合理相关性的评估(21 CFR 312.64)。申办者需向FDA和所有参与研究者报告非预期可疑严重不良反应(21 CFR 312.32(c)(1)。方案应规定安全界限，并描述不良事件后受试者随访的类型和持续时间。也就是说，将这些信息(发生的开始和结束时间)均记录在CRFs上是明智的。请注意，所有事件都需要记录，但不是所有事件都需要报告。Under FDA regulations, the investigator is required to report serious adverse events to the sponsor and must include an assessment of whether there is a reasonable possibility that the drug caused the event (21 CFR 312.64). The sponsor is required to report serious and unexpected suspected adverse reactions to FDA and all participating investigators (21 CFR 312.32(c)(1). The protocol should specify the safety parameters, and describe the type and duration of the follow-up of subjects after adverse events. That said it seems prudent that the information (start and end time of the occurrence) is generally captured on the CRFs. Please remember that all events need to be recorded but not all need to be reported.与这个问题相关的讨论体现在FDA指南草案“INDs和BA/BE研究的安全报告要求”中(可在www.fda.gov/downloads/Drugs/…/Guidances/UCM227351.pdf 中找到)。该指南草案与FDA 2010年9月29日发布的最终规则“人类药物和生物制品的试验性新药安全报告要求”一致。有关这一最终规则的信息可通过以下链接获得: www.fda.gov/drugs /DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/ ationalnewdrugindapplication /ucm226358.htm。A discussion related to this issue occurs in FDA's draft guidance "Safety Reporting Requirements for INDs and BA/BE Studies" (available at www.fda.gov/downloads/Drugs/.../Guidances/UCM227351.pdf ). This draft guidance was issued in concert with FDA's final rule, which published on September 29, 2010, "Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products." Information on this final rule is available at the following link: www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/ucm226358.htm.如果我没有充分回答你的问题，你可以直接联系药物中心(CDER)，医疗政策办公室(OMP)。CDEROMP@fda.hhs.govIf I have not adequately answered your questions, you may contact the Center for Drugs (CDER), Office of Medical Policy (OMP) directly. CDEROMP@fda.hhs.gov
译自FDA Good Clinical Practice (GCP) Q&A
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