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MHRA GXP Data Integrity Guidance: Part 1 - A GCP Perspective MHRA GXP数据完整性指南：第一部分—GCP视角 Posted by: Paula Walker,Posted on: 6 March 2019 - Categories: Compliance matters, Good clinical practice 发布：Paula Walker 发布时间：20190306 分类：合规事务，优良临床规范 The MHRA published the GXP Data Integrity Guidancein March 2018 (see post). Thiswas welcomed by industry and has been discussed at many stakeholder eventssince. As part of our engagement with stakeholders, we welcome feedbackon guidance issued and the Data Integrity (DI) guidance is no exception. As such, we will be issuing a series of GXP blog posts to assist further on thereflections received since the issuance of the guidance. MHRA于2018年3月发布了GXP数据完整性指南。该指南受到企业欢迎，有许多干系方对此进行了讨论。作为我们与干系人互动的一部分，我们欢迎对所发布指南提供反馈，DI指南亦不例外。在此，我们将发布一系列的GXP博客，对指南发布以来所收到的反思进行深入探讨。 This series of posts starts with the Good ClinicalPractice (GCP) perspective. We have been made aware of some clarificationneeded in the interpretation and implementation of the GXP DI guidance in theclinical trial setting, which we hope to clarify via this post. 本系列博客将从优良临床规范（GCP）角度开始。我们了解临床试验环境中GXPDI指南诠释与实施需要一些说明，我们希望通过此博客可以作出一些解释。 Audit TrailReview 审计追踪审核 The guidance describes the need for a documentedaudit trail review, where the need for and extent of such evaluation isidentified in the trial risk assessment, performed prior to the trialcommencing. This could include evaluation of data points associated withcritical/complex trial processes, in other words, where the trial risksare. This has led many to question whether this means that sponsors, orindeed Clinical Research Organisations (CROs) working on behalf of sponsors, needto develop a generic audit trail review Standard Operating Procedure (SOP) thatcovers this process, that is, an SOP not specific to a particular clinicaltrial as part of their quality system. To answer this question, we wouldrefer organisations back to the statement that the need for a review of anaudit trail should be determined by a risk assessment based on the requirementsof the trial, taking into account the systems, procedures and controls in placeto be used in the trial. Therefore, to have a generic SOP would probablynot add any benefit to this process and is not mandated by the guidance orexpected by GCP inspectors. 指南中讲了需要有书面的审计追踪审核，在试验开始之前所进行的试验风险评估中识别是否需要此评估及其程度。其中可能包括对数据点以及关键/复杂试验流程的评估，换句话说，识别哪些方面有试验风险。这样可能会导致许多人质疑这是否意味着发起人，或实际上是代表发起人的临床研究机构（CRO），需要制订一份通用的审订追踪审核SOP覆盖此流程，也就是说，制订一份不专属于某特殊临床试验的SOP作为其质量体系的一部分。为了回答这个问题，我们要引导机构回去看看具体说法，对于审计追踪是否需要进行审核应根据试验的要求应由风险评估来确定，同时考虑在试验中所用的已有系统、程序和控制。因此，有一份通用的SOP可能不会对此流程带来好处，并且指南也没有此强制要求，GCP稽查员亦并不要求。 It should be noted that the audit trail reviewreferred to in the DI guidance refers to those data collection activities thathave a formal computer-generated audit trail. Other ways of demonstratingdata integrity and reconstruction of the life cycle of a record are of coursepossible where other ways of collecting data are used. 要注意的是审计追踪审核在DI指南中指的是具有正式计算机生成审计追踪的数据采集活动。如果采用其它方式采集数据，自然可能在记录的生命周期中采用其它方式证明数据完整性和可重构性。 Conducting a trial risk assessment upfront has longbeen recommended by the MHRA GCP inspectors as a way of identifying andmitigating all risks associated with your clinical trial (see Risk Adaptation post), and this is supported bythe ICH E6 (R2) Addendum. This risk assessment should addressthe most appropriate approach to demonstrating the integrity of the datarequired by the clinical trial protocol. That is, the risk assessment fordata integrity can be incorporated into the standard trial risk assessment anddoes not necessitate a separate document/duplicate of information alreadycontained within the overall trial risk assessment. MHRA GCP稽查员一直建议将预先进行试验风险评估作为识别和降低所有与临床试验有关风险的一种方法，并且ICH E6（R2）亦支持此方法。此种风险评估应说明证明临床试验方案所需数据的完整性的最恰当方法。也就是说，数据完整性的风险评估可包括在标准试验风险评估中，而不需要单独记录/重复在整体试验风险评估中已包括的信息。 Recordingof Patient Data 记录患者数据 We have been asked what the practical implicationsof the DI guidance are in the clinical setting, in particular in relation torecording of patient data, and the need for a second person to verify, forexample, vital signs from the recording instrument, as has been theinterpretation by some organisations. Section 5.2 of the DI guidancestates that ‘recording by the second person should be contemporaneous withthe task being performed, and the records should identify both the personperforming the task and the person completing the record’. From theclinical and GCP perspective it is of course common practice for one person, aspart of standard medical care, to take readings from instruments not equippedwith a computerised data system or recording device, such as athermometer. In such standard clinical situations occurring in clinicaltrials, this can absolutely be the same person performing the task andcompleting the clinical trial record. A second person would only be neededif, from a clinical perspective, it is not practical for one person to bothperform the clinical tasks and record the data. There is absolutely noexpectation from the DI guidance to have 2 people responsible for this. 曾有人问我们，DI指南在临床设置中有何实践含义，尤其是在记录患者数据方面，以及是否需要第二人复核，例如，记录仪器的实时签名，因为有些组织是这样解释的。DI指南的第5.2部分说“第二人记录应在任务实施时同步记录，记录中应辨明执行任务与完成记录的人的身份”。从临床和GCP角度来说，作为标准医护操作的一部分，常见做法是一个人从未配置计算机化数据系统或记录仪器的仪器仪表中读取数据，例如，温度计。在临床试验的此种标准诊疗情形中，这绝对是等同于由同一人执行任务并完成临床试验记录。从临床角度来说，只有当一个人无法同时执行临床任务和记录数据时才需要有第二人参与。DI指南的本意绝对不是要求在这时必须有2个人。 Amount andResolution of Data to be Collected 要采集的数据数量和层级 We have been asked, in the GCP context, exactlywhat it means to collect data that ‘allows the full reconstruction ofactivities, the amount and the resolution (degree of detail) of data to becollected’, as per section 6.7 of the DI guidance. Concern has beenraised that this may mean organisations (whether sponsor/CRO/contractedorganisation) should be developing a stand-alone SOP for determining the amountand resolution of data to be collected. 曾有人问我们，在GCP环境下，根据DI指南第6.7部分，采集数据“允许全面重构活动，要采集的数据的数量和层级（详细程度）”的确切含义是什么。有人担心这是不是表示组织（发起人/CRO/合同机构）应制订单独的SOP来确定要采集的数据的数量和层级。 Determining the amount and resolution of the datato be collected is an integral part of clinical trial quality/data managementas defined by ICH E6(R2). The precision, accuracy and timing of clinicalmeasurements are determined by the authorised clinical trial protocol and arecommonly addressed and documented as part of an organisation’s overall qualitymanagement planning, rather than specifically in relation to any ‘separate’ DIconsiderations. Therefore, it is up to organisations to determine thebest way to approach this as per their quality system, and there is nostatutory requirement to have a stand-alone SOP. 按ICH E6（R2）的定义，确定要采集的数据的数量和层级是临床试验质量/数据管理不可分割的一部分。临床测定的精密度、准确度和时效性是由批准的临床试验方案决定的，通常会解释和记录成为机构全面质量管理规划的一部分，而不是与任何“单独的”DI考量有特别关系。所以应该由机构根据其质量体系决定最佳方法是什么，也没有强制要求说必须制订一份单独的SOP。 Overall, the important message of this post is thatthe GXP DI Guidance introduces no new statutory requirements for clinicaltrials, or specific requirements for mandatory SOPs. As with all relevantguidance there is an expectation that this is followed (as per ‘Theinvestigator and sponsor shall consider all relevant guidance with respect tocommencing and conducting a clinical trial’ Schedule 1, Part 2(8): UK ClinicalTrials Regulations 2004, as amended). 总体来说，此博文要传达的重要信息是GXP DI指南并没有引入新的临床试验法规要求，或者是强制SOP的特殊要求。与所有相关指南一样，只是需要遵守一定的要求（根据“调查员和发起人应考虑与启动和执行临床试验有关的所有指南”，英国临床试验法，2004，及其修订案，第2（8）部分第1条）。 How the guidance is implemented, however, should bedetermined by an organisation’s existing quality system, the need foradditional procedures determined by the requirements of an individual trial orscope of work, and should not require duplication of existing SOPs or ways ofworking simply to fulfil the perceived needs of the DI guidance. 总之，应该由组织自己现有的质量体系决定如何执行该指南，是否需要制订另外的程序是由各试验或工作范围的要求来决定的，不应该仅为了满足DI指南中的需求而要求制订与现有SOP或工作方法重复的程序。 If you have specific queries regarding this you cancontact the Clinical Trial Helpline (ctdhelpline@mhra.gov.uk) or, to discusswith fellow stakeholders how they are approaching this area, the MHRA GCP Forum is a good informal environment touse. 如果你有关于此方面的特殊问询，可联络临床试验帮助邮箱，或与干系人讨论他们在此领域的方法，MHRA GCP论坛是个获取信息的好地方。 We would like to thank the Association of ClinicalResearch Organisations (ACRO) for their feedback and input into this discussionfrom the CROs that they represent. 在此感谢临床研究机构协会（ACRO）代表其CRO对此讨论的反馈和建议。 |
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