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Tuesday, November 22, 2022 | 2:52 PM
Essential Documents: According to ICH GCP Section 8, “Essential documents are those documents that individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor, and monitor with the standards of GCP and with all applicable regulatory requirements.” Simply stated, essential documents are documents that are needed to recreate the trial and its results. Section R8 provides us with some guidance on the types of documents that are essential to recreate the trial and demonstrate integrity of the trial data. However, this is not an inclusive list, and it needs consideration to determine which documents are expected vs. required during TMF setup.
Essential Documents and the TMF Reference Model: The TMF Reference Model is a crucial tool in building upon the minimum list defined by ICH GCP. As well as providing an industry standard on the content of a TMF, standard naming, metadata, and structure, the TMF Reference Model also defines “core” and “recommended” artifacts. An artifact that must be filed in the TMF based on a regulatory requirement, ICH GCP, or based on guidance from the TMF Reference Model group, would be listed as “core.” The TMF Reference Model even goes as far as providing the ICH GCP reference for each artifact. Artifacts labeled “recommended” are documents that do not have to be generated but should be filed in the TMF if created. For further information on essential documents, refer to TransPerfect’s "Back to the Basics" blog.
Expected and Required Documents: The terms “Essential/Expected Document List” (EDL and “Required Document List” (RDL) are commonly used interchangeably in the industry. The requirement to collect documents listed as “core” could be dependent on the phase, therapeutic area, or type of study being conducted (e.g., device vs. drug study). Just because a document is labeled as “core” in the TMF Reference Model doesn’t mean it is required if the document is not applicable based on the study design. Documents labeled as “recommended,” although not defined as essential, are important for indicating how the study is conducted.
Other Factors: Expected or required documents can also be driven by the countries participating in the study based on country-specific regulatory requirements. Documents can be deemed expected or required based on sponsor and CRO SOPs and processes. Therefore, it is important to factor these specifics into your overall expected or required list.
Required Documents and Events and Milestones: It is important to remember that expected and required documents are not only defined at the start of the study. They should be constantly monitored and updated based on changes to the study, such as with regard to events or milestones. An event, such as a protocol amendment, could make a document initially marked as “not required” or “expected” become an essential document, not only impacting site documents but country and trial levels as well.
Required Documents and Completeness: In order to measure TMF completeness, it is essential to know what is expected and required for your study.
TMF RM & essential documents defined by ICH GCP + study-specific design + study-specific requirements + events & milestones + collected documents = TMF completeness.
A Step in the Right Direction for Clinical Trial Management: Improvements on the GCP E6(R3) ICH Harmonized Guidelines