分享 ▎纸质版AE记录表和相应CRF记录页的签署
分享 ▎纸质版AE记录表和相应CRF记录页的签署
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纸质版 AE 记录表和相应C RF 记录页的签署
Signing of Paper AE Logs and CRFs
2019 年 11 月 08 日
N ov 08, 2019
问题Question
您好，
我一直在寻找关于研究者在临床试验AE记录表或 AE CRF 记录页上签字以确认审核和批准的时间（日期）的规定。关于 AE ，所有的申办者都要求有清晰和完整的源文件记录。签署 S AE 的时间也是非常明确的。然而，对于非严重的AE，对于要求研究者签署的时间是不明确的。对于与肿瘤相关的临床试验，许多申办者要求研究者在下一个给药周期开始前 （通常为 21 至 28 天）对 AE 记录表或 AE CRF 记录页进行审查并签字。其他试验，申办者则要求在 5 天或 7 天内完成。
我知道FDA对签名的要求很少（比如知情同意书和 1572 表格）；但是，是否有任何关于这个（签署）时间的规定或 GCP 指南。我好像没能找到。
Hello,
I have been looking for regulations regarding the timing (# of days) that the investigator musty sign the research AE Log or AE CRFs thereby acknowledging their review and approval. All sponsors require clear and thorough source documentation regarding the AE. The timing is also very clear on signing off on Serious Adverse Events. However, for non-serious AEs, the timing differs on when the investigator is required to sign off is inconsistent. For cancer related trials, many sponsors are asking for them to be reviewed and signed by the investigator by the time of initiation of the next cycle of drug admin126459646istration (generally 21 to 28 days). Other sponsors are requiring it within 5 or 7 days.
I know the FDA has few signature requirements (i.e.. ICF and 1572); however, is there any regulations or GCP guidance regarding this timing. I cant seem to find any.
Thank you again.
回答Answer
上午好，
我们的规定要求 “……试验活动中的所有变化以及所有涉及人类受试者或其他人风险的非预期问题……”应“及时”向 IRB 报告。 （参见 21 CFR 312.66. ） 此外，我们的法规要求各 IRB “遵循书面流程，以确保及时向 IRB 报告……【任何】涉及人类受试者或其他人风险的非预期问题……”（参见 21 CFR 56.108 （ b ） ）。
因此，各 I RB 在制定适当的时限要求以确定何时向他们提交安全信息以及确定哪些报告应尽早提交的时候，有一定的决定权。这些时限要求，以及任何其他对于格式或其他应该提供给他们的信息的要求，通常在各 IRB 的 sop 或其他规定中予以描述。
FDA 的规定还要求在报告“严重和非预期”的 AE 时，要有与试验产品的关系 （判断 ），参见 21 CFR 312.32 ， 尤其是 21 CFR 312.32 （ c ）（ 1 ）（ i ）（ A ）， “申办者应以书面 IND 安全报告的形式告知 FDA 和所有参与研究者任何与该药物使用相关的严重和非预期的不良事件……”
第 0 天，相对于 IND 安全报告的第 7 天和第 15 天，是申办者（或根据《 21 CFR 312.52 》申办者将义务转移给了 CRO ）确定的信息可以报告的日期。在 CRO 来收集不良事件信息的情况下，正式法规中没有规定条款允许额外的时间给需快速上报的 I ND 安全报告。
请参见 F DA 关于 A E 报告的指南
https://www.fda.gov/media/72267/download
https://www.fda.gov/media/79394/download
Questions and Answers on FDA’s Adverse Event Reporting System (FAERS) | FDA
FDA法规的确没有提到 AE 记录表的签署时间问题。
如果我没有充分回答你的问题，你可以联系CDEROMP CDEROMP@fda.hhs.gov，因为他们是 AE 报告方面的专家。
Good morning -
Our regulations require that "...all changes in the research activity and all unanticipated problems involving risk to human subjects or others..." be reported "promptly" to the IRB. (See 21 CFR 312.66.) In addition, our regulations require that IRBs "follow written procedures for ensuring prompt reporting to the IRB...of [any] unanticipated problems involving risks to human subjects or others..." (See 21 CFR 56.108(b). )
Thus, IRBs have some discretion in establishing appropriate timeframes for when safety information should be submitted to them, and for identifying the reports that should be submitted sooner rather than later. Such timeframes, as well as any other expectations as to the format or other information that should be provided to them, are generally described in each IRB’s SOPs or other policy guidelines.
FDA’s regulations also require an association with the test article for reporting of AEs that are both "serious and unexpected." See 21 CFR 312.32, in particular, 21 CFR 312.32(c)(1)(i)(A), "The sponsor shall notify FDA and all participating investigators in a written IND safety report of (A) Any adverse experience ASSOCIATED WITH THE USE OF THE DRUG that is both serious and unexpected..."
Day zero, for both 7 day and 15 day IND safety reports, is the day the sponsor (or CRO to whom a sponsor has transferred an obligation per 21 CFR 312.52) determines that the information qualifies for reporting. There is no provision in the final rule to allow for additional time for expedited IND safety reporting in cases in which a CRO collects adverse event information.
Please see FDA guidance on AE reporting –
https://www.fda.gov/media/72267/download
https://www.fda.gov/media/79394/download
Questions and Answers on FDA’s Adverse Event Reporting System (FAERS) | FDA
FDA regulations do not address the timing of signing the AE log.
If I have not adequately answered your question, you may contact CDER OMP at CDEROMP@fda.hhs.gov as they are the experts on AE reporting.
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