Drug Evaluation Committee June 2023: Regarding the Scope of ALCOA
Related Category: Other
Initial Publication Date: August 2023
Question
I feel that the application of ALCOA principles when creating and revising source documents has become quite well-established in Japan. On the other hand, some people believe that ALCOA is required for all documents, which I believe may be leading to an increased burden on medical institutions.According to the GCP Operational Notice, “source documents” refer to records necessary for reconstructing and evaluating the factual course of a clinical trial, such as medical records pertaining to subjects, examination notes, and records of administration of investigational drugs.
Looking solely at the phrase “records necessary for the reconstruction and evaluation of the factual course of the clinical trial,” one might interpret this to mean all documents generated during a clinical trial. However, what exactly is the scope of the records necessary for the reconstruction and evaluation of the factual course?
For example, if an administration record for an investigational drug (which serves as the basis for the CRF) is created using a worksheet, is an ALCOA also required for corrections to the investigational drug management sheet (which does not serve as the basis for the CRF)?Since many of the materials available online cite subjects’ medical data as examples, I would appreciate your opinion on whether administrative documents related to clinical trials, as well as documents that do not serve as the basis for CRFs or physicians’ judgments, fall under the category of “records necessary for the reconstruction and evaluation of factual events.”
JPMA Opinion
As defined in Guidance Note 6 of Article 2 of GCP, “source documents are documents, data, and records that serve as the basis for information regarding the factual course of a clinical trial, such as case report forms,” all records related to clinical trials created at medical institutions can constitute source documents. “Raw data” included in source documents is defined in Guidance Note 18 (12) of the same article as“all information recorded in the original records and certified copies thereof regarding clinical findings, observations, and other activities in a clinical trial, which is necessary for the reconstruction and evaluation of the factual course of the clinical trial,” and Article 41, Paragraph 1, Item 4 of GCP further stipulates that raw data must satisfy the ALCOA criteria.Furthermore, since Article 21, Paragraph 1, Item 9(11) of GCP defines the monitor’s role as “confirming that all clinical trial-related records, such as source documents, are accurate, complete, and up-to-date,” all source documents (including source data) must be created in accordance with the ALCOA principles.
Regarding the examples cited in your question—the administration records for the investigational drug on the worksheet (which serve as the basis for the CRF) and the investigational drug management table (which does not serve as the basis for the CRF)—if the information recorded constitutes source data, these serve as records that reconstruct the administration history,and a record that reconstructs the receipt and dispensing of the investigational drug, respectively, and therefore must be prepared in accordance with ALCOA.