【FDA Q&A 24/25版】在无法访问电子病历的情况下,什么可视为充分的源文件?

10.3 Q. What ramification(s) are involved if a regulatory inspection was to occur for cases where the investigative site will only provide copies of electronic medical records and not allow direct/indirect access to the study monitor or regulatory inspector? What is considered adequate source documentation in lieu of no access to the electronic medical records?

10.3 问：如果研究中心只提供电子病历副本，不允许监查员或监管检查员直接/间接访问，那么若发生监管检查会有什么后果？在无法访问电子病历的情况下，什么可视为充分的源文件？

A. Many institutions and sites are going to a fully electronic record system. If certified copies of the medical records are not made, monitors and auditors will want to at least spot check the completeness of these records at the source - the electronic database or the EMR. How they are viewed is at the institution’s discretion. However, either looking over the shoulder of a study staff member or having limited access to the medical records is common.

答：许多机构和研究中心正全面转向电子记录系统。如果未制作医疗记录的核证副本，监查员和稽查员至少希望在源头——电子数据库或电子病历——抽查这些记录的完整性。如何查看这些记录由机构自行决定。然而，监查员在研究人员身旁查看其操作，或获得有限的医疗记录访问权限，是常见做法。

The reason at least a spot check is necessary is that the records can be selectively copied. So even though they are certified copies they may not be complete records. The monitor/auditor is checking to ensure that study inclusion/exclusion are met and that there are no concomitant issues that would preclude the individual’s participation in the study or confound the results.

至少需要抽查，是因为记录可能被选择性复制。因此，即使它们是核证副本，也可能不是完整记录。监查员/稽查员正在核查，以确保符合入组/排除标准，并且不存在妨碍个体参与研究或混杂结果的伴随问题。

In general, during an inspection the agency usually reviews original (source) records or certified copies of clinical trial records. For example, during an inspection of a clinical investigator (CI), the regulatory investigator will evaluate the CI’s practices and procedures to determine compliance with applicable regulations. Quite often CIs maintain copies of certain records in their study files, e.g., records from a hospital or other institution that must maintain the originals. FDA refers to these as shadow files. While it is acceptable to keep shadow files in the study records, should FDA conduct a bioresearch monitoring (BIMO) inspection of the study in question, the FDA investigator will expect to review at least a portion of the original source documents for such shadow files to verify their authenticity, even if the copies in the shadow files are certified as authentic copies. During a regulatory inspection, the eTMF may be inspected for part 11 compliance.

一般而言，检查期间机构通常会审查原始（源）记录或临床试验记录的核证副本。例如，对临床研究者（CI）进行检查时，监管检查员会评估CI的做法和流程，以确定是否符合适用法规。临床研究者常会在其研究文件中保存某些记录的副本，例如来自必须保存原件的医院或其他机构的记录。FDA将其称为影子文件。虽然研究记录中保留影子文件是可接受的，但如果FDA对相关研究进行生物研究监测（BIMO）检查，FDA检查员仍会期望审阅此类影子文件至少一部分原始源文件，以核实其真实性，即使影子文件中的副本被认证为真实副本。在监管检查期间，eTMF可能接受Part 11符合性检查。

In a June 2010 FDA Information Sheet titled, “FDA Inspections of Clinical Investigators,” the agency briefly addresses the topic of inspecting pre-study records. “FDA may also examine subjects’ medical records that are part of the clinical investigation and predate the study to verify whether the condition under study was in fact diagnosed, the study eligibility criteria were met, and whether the subject received any potentially interfering medication prohibited by the protocol. The FDA investigator may also review subjects’ records covering a period after completion of study-related activities to determine if there was proper follow-up as outlined in the protocol, and if the clinical investigator submitted all reportable adverse events (including all clinical signs and symptoms).”

在2010年6月一份题为“FDA对临床研究者的检查”的信息表中，该机构简要说明了检查研究前记录的问题：“FDA还可检查属于临床研究一部分且早于研究的受试者医疗记录，以核实所研究疾病是否确实得到诊断、研究入组标准是否满足，以及受试者是否接受过方案禁止的任何可能产生干扰的药物。FDA检查员还可审查研究相关活动完成后一段时期内受试者的记录，以确定是否按方案规定进行了适当随访，以及临床研究者是否提交了所有可报告的不良事件（包括所有临床体征和症状）。”

Regarding the creation of certified copies of source documents, ICH E6 (R3) Draft defines a certified copy as “a copy (irrespective of the type of media used) of the original record that has been verified (i.e., by a dated signature by generation through a validated process) to have the same information as the original, including relevant metadata, where applicable.” The use of certified copies generally applies to situations where original records are copied to a different media for archiving purposes and the originals are destroyed. However, if it is decided to have a certified copy substitute for the original, it would be desirable to have a “standard operating procedure” (SOP) describing how such copies would be made, verified, and documented. The person who certifies the copy as an same person who actually made the copy from the original. Certification should be accomplished by having the person who makes the copy, sign or initial and date the copy to indicate it meets the requirements of a certified copy as described above. This should be described in the SOP and can be accomplished by initialing and dating each copy or by initialing and dating a document certifying copies in bulk. Whichever method is used, the SOP should describe the procedure.

关于源文件核证副本的制作，ICH E6（R3）草案将核证副本定义为：“原始记录的副本（不论所用介质类型），该副本已经过验证（即通过经验证的流程生成并附有注明日期的签名），证明其与原始记录包含相同信息，包括适用时的相关元数据。”核证副本的使用通常适用于为存档目的将原始记录复制到不同介质并销毁原件的情形。然而，如果决定以核证副本替代原件，最好制定标准操作程序（SOP），说明此类副本如何制作、验证和记录。认证该副本的人应为实际从原件制作该副本的同一人。认证应通过由制作副本的人在副本上签名或签姓名首字母并注明日期来完成，以表明其符合上述核证副本要求。这一点应在SOP中说明；可通过在每份副本上签首字母并注明日期，或在一份批量认证副本的文件上签首字母并注明日期来完成。无论采用哪种方法，SOP均应描述该程序。

Burning a CD at the end of the study, converting e-mails into a PDF format or adopting a procedure to make certified copies are all acceptable methods to achieve study related documents. A company just needs to make certain that whatever media it uses does so in a manner that preserves the integrity of the original data/information.
研究结束时刻录CD、将电子邮件转换为PDF格式，或采用制作核证副本的程序，都是形成/保存研究相关文件的可接受方法。公司只需确保无论使用何种介质，均以能保持原始数据/信息完整性的方式处理。