Drug Evaluation Committee 2011-46 Identification of source documents - Documents that are directly entered in case report forms and should be interpreted as source data
Related classification: Record keeping
First published: Apr. 2012
Revised publication date: December 2021
Question
The protocol for a clinical trial currently underway stipulates that "the reason for denial of causal relationship of an adverse event shall be entered in the EDC as the source data". On the other hand, the EDC used in this clinical trial allows the CRC to enter "reasons for denial of causal relationship of adverse events. In fact, at our hospital, the investigator or sub-investigator records the "reason for denial of causal relationship of adverse event" on a worksheet in the medical record, and the CRC transcribes this information from the record into the EDC. Is this method problematic?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
Article 2, Paragraph 17 of the GCP defines "'Case report' means a document that describes the data of the source material and the investigator's or subinvestigator's or post-marketing clinical trial investigator's or subinvestigator's evaluation of it for each subject." This is defined as "a document that describes the data of the source documents and the evaluation of the investigator or subinvestigator or post-marketing clinical trial investigator or post-marketing clinical trial subinvestigator on each subject. In contrast, Article 47, Paragraph 1 of the GCP stipulates that "the investigator shall accurately prepare the case report form in accordance with the protocol. In accordance with Article 43, Paragraph 1, Guidance 1 of the GCP, the investigator may share part of the work of preparing the case report form.
On the other hand, in the clinical trial in question, the "reason for denial of causal relationship of adverse events" is based on the Central Pharmaceutical Affairs Council Report (No. 40, March 13, 1997, Central Pharmaceutical Affairs Council) 10-4 9) "Identification of materials directly entered in the case report form (that is, no data recorded in written or electronic form before such entry) and which should be interpreted as original data. We believe that this provision is based on the "identification of materials that are directly entered in the case report form (i.e., no documented or electronically recorded data prior to the entry) and that should be interpreted as original data.
In your hospital, the standard procedure is that the "reason for denial of causal relationship of the adverse event" is recorded in the medical record by the investigator, etc. Therefore, the data from the source material of the "reason for denial of causal relationship of the adverse event" (i.e., the source data) is considered to be the record in the medical record. If the original data is transcribed into the EDC, there should be no problem.
The provision in the protocol is based on the assumption that the reasons for causal relationships for all adverse events are not necessarily recorded in the medical record. We recommend that you confirm the interpretation of the protocol with the sponsor and identify source documents (determine standard procedures) before starting the clinical trial.
Reason for revision of opinion
With the issuance of the GCP Ministerial Ordinance (August 31, 2020, Ministry of Health, Labor and Welfare Ordinance No. 155), the provisions to be referred to have been changed.