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NTF在哪些方面被过度使用?| GCP Q&A 6.15

Q.In what ways are notes to file overused, and what are considered to be inappropriate uses of
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Q.
6.15 问:
A. There seems to be a growing consensus among industry clinical research professionals that ‘notes to file’, while useful, have been overused. Although such notes can be an important tool in documenting a study-related issue, as well as helping monitors, auditors and inspectors reconstruct how a study was conducted, the overuse of ‘notes to file’ (NTF) can raise questions.
答:。临床研究行业的专业人员之间越来越多的共识似乎是:“说明文件”虽然有用,但已被过度使用。尽管此类说明可能是记录与研究相关的问题的重要工具,并且可以帮助监查员、稽查员和检查员重构研究进行的方式,但过度使用“说明文件”(NTF)可能会引发一些问题。
When a significant number of ‘Notes to File ‘are observed during a field inspection, it may be an indicator of poor oversight, inadequate training of study coordinators, overly taxing workload, of simply sloppy record keeping. In any event, when a note to file contradicts other study documentation, it can be damaging in an inspector’s assessment of a study. Examples of inappropriate uses for notes to file (NTF) include many situations in which the subjects of the notes have already been addressed sufficiently in other study-related documentation. Some examples of the use and overuse of notes to file include the following:
当在现场检查中发现大量的“说明文件”时,可能表明监管不力,研究协调员的培训不足,工作量过大,保存记录草率。无论如何,当说明文件与其他研究文件相抵触时,都可能导致检查员对研究的评估造成损害。说明文件(NTF)不当使用的例子,包括与说明主题相关的多种情境,已在其他与研究相关的文件中得到了充分解决。以下是一些使用和过度使用说明文件的示例:
• The author of an NTF placed in the site study file should accurately and concisely outline in detail the (1) issue, (2) site action or inaction, (3) purpose requiring note clarification. Because this issue involves a site action/inaction, the author of the NTF should be a member of the site staff (the clinical investigator or appropriate delegate). There are isolated cases in which a Sponsor or designee may enter a NTF that must be included in the site master file, these may include letters, faxes, emails, memos regarding sponsor services; protocol exception granted (specific to a certain site); clarification of completion of a certain page of CRF (to all sites)).
• 存放于中心研究文件中的NTF中,作者应准确、简洁、详细地概述(1)问题,(2)中心采取或未采取的行动,(3)阐明需要说明的目的。由于此问题涉及中心采取或未采取的行动,因此NTF的作者应为中心工作人员(临床研究人员或适当的代表)中的一员。在个别情况下,申办方或被被委派的人可能中心文件夹中保存NTF(必要时),其中可能包括信函、传真、电子邮件、关于申办方服务的备忘录;方案例外授权(具体到某个中心);澄清完成的CRF的某一页(对于所有机构))。
• A site deficiency has already been documented in another format and the NTF is repetitive. For example, if the source documents note that the patient failed to take study medication as required by the protocol and that the patient was reinstructed, a note to file documenting this would be repetitive. Also, actions to be taken to assess whether the re-teaching was effective could be written directly in the source documentation.
• 中心的不足之处已经以另一种格式进行了记录,所以NTF是重复的。例如,如果源文件记录了患者未能按照方案要求服用研究药物,并且患者已被重新训练,则说明文件(说明此事件的)的记录将是重复的。同样,也可以在源文件中直接编写评估该患者的重新训练采取的行动是否有效。
• Assume that a site did not consent the patient on the correct version of the informed consent, but that the site contacted the IRB by email about the error, stating that it has scheduled a patient visit on a specific date for re-consenting and that it has implemented a specific plan to prevent a repeat of such cases. In this case, the existing documentation would be sufficient, and a note to file repeating this would be repetitive.
假设某中心不赞成患者知情同意书的正确版本,但该机构已通过电子邮件与IRB联系并告知该错误,同时阐明该中心已安排在特定日期让患者重新进行知情同意,且已经实施了一项具体计划,以防止再次发生此类情况。在这种情况下,现有的文档就足够了,再次说明此事的说明文件将是重复的。
An NTF documenting that the patient was not properly consented prior to study procedures being initiated. The error is noted and is signed by the clinical research coordinator and placed in the subject’s study file. First, the NTF content is not valuable when it simply points out the error. To be valuable documentation, the NTF should also include why this happened, the actions that were taken/will be taken to address the deficiency, the steps that will be taken to prevent this situation from recurring, and how the effectiveness of the intervention will be evaluated. Secondly, the content level of the NTF dictates that the principal investigator author the note. While the third party can template the NTF, the investigator really must review, approve and sign the note due to the severity of the issue.
NTF记录在开始研究程序之前患者未获得恰当的知情同意。该错误已记录下来,并由临床研究协调员签名并放置在受试者的研究档案中。首先,当NTF内容仅仅只是简单指出错误是没有价值的。作为有价值的文件,NTF还应包括其发生原因、为解决缺陷所采取的或将要采取的行动、为防止这种情况再次发生而将采取的措施以及评估干预措施的有效性。其次,NTF的内容层面要求由主要研究者撰写该说明。尽管第三方可以为NTF提供模板,但由于问题的重要性,研究者确实必须审核,批准并签署说明文件。
Over the past several years, multiple warning letters issued by the FDA have cited sponsors’ use of notes to file, noting that these memos were insufficient to address specific issues or were inadequate, in and of themselves, to secure compliance at trial sites. In a warning letter, the FDA stated that, “our investigation found that [the sponsor] failed to take any action to secure compliance while the study was ongoing except to generate numerous memos to the file after all the subjects had completed the study…,” in the 2007 letter, FDA states “We note that generation of numerous memos to file after all subjects have completed the study does not adequately secure compliance of an investigator.” Although the sponsor indicated to the FDA that the memos to file were used “as a mechanism to train the investigator,” the sponsor conceded that the value was limited given that the majority of the memos were generated after all subjects had completed the study.
在过去的几年中,FDA发出的多封警告信都引用了申办方对说明文件的使用,并指出这些说明不足以解决特定问题,或者本身不足以确保试验现场的合规性。FDA在2007年的一封警告信中表示:“我们的调查发现,[申办方]在研究进行中没有采取任何措施确保合规性,只是在所有受试者完成研究后生成大量NTF文件……”,“我们注意到,在所有受试者完成研究后生成的大量NTF不足以确保研究的合规性。”尽管申办方向FDA表示备案的NTF被“用作培训研究人员的一种途径”,但申办方也承认,由于大部分NTF是在所有受试者完成研究后生成的,因此其价值是有限的。
It has been noted that while NTF’s may identify issues, errors or problems observed at a site, they fail to address what the sponsor/site did to resolve the deficiency and to prevent reoccurrence in the future. Issue resolution should be a closed loop system in which the problem is identified, cause is determined, mitigation strategies are implemented, and results are documented and shared as “lessons learned”.
值得注意的是,尽管NTF可能会指出在中心发现的异常、错误或问题,但它们无法去指明(阐述)申办方或中心为解决问题和防止将来此类问题再次发生所做的工作。问题解决应是一个闭环系统,包括识别问题、确定原因、执行解决策略以及记录结果并作为“经验教训”进行共享。
发布于 2021-12-05 20:55:43 © 著作权归作者所有
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