Drug Evaluation Committee 2019-40 Identification of source documents - Materials that are directly entered in case report forms and should be interpreted as source data (Part 2)
Related classification: Record keeping
Date of first publication: December 2019
Question
In outcome studies, it is stipulated in the study protocol that interviews (statements themselves) from subjects are entered into the EDC on the spot, without using medical records or worksheets. The results of vital measurements, etc., are also required to be entered directly into the EDC and are not allowed in the medical record. In this case, the CRC will directly input the content of interviews and test values from the subject into the EDC, and the EDC will be the first record. Since the source data is not recorded in the medical record or worksheet, the reproducibility of the clinical trial is difficult. Is there any problem with a situation where the source data does not remain at the implementing institution?
Also, with regard to adverse events, the CRC is required to enter the event name and causal relationship into the EDC on the spot based on interviews with the subject. It seems that the EDC (interview with the subject) is later confirmed by the investigator, etc. to ensure medical judgment, but is this procedure where the CRC enters the EDC with medical judgment at the first record stage appropriate?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
GCP (GCP Article 7, Paragraph 1, Guidance 2/Central Pharmaceutical Affairs Council Report 10-4 9) and ICH-GCP 6.4.9) requires "identification of materials that are directly entered in the case report form (i.e., no data recorded in written or electronic form before such entry) and should be interpreted as source data" as a provision of the clinical study protocol. This form of recording is also permitted under the current GCP. However, this identification should be carefully considered, taking into account the method of obtaining and recording data, including tests.
On the other hand, the original data must satisfy attribution, legibility, contemporaneity, originality, accuracy, and completeness. If the original data is changed, the process can be traced back and the description before the change should not be unclear. In addition, such changes should be explainable, if necessary (GCP Article 41, Paragraph 1, Guidance 4). Furthermore, since the source documents are records that the site is obligated to preserve and is authorized to manage, the sponsor should not exclusively manage them, but should ensure that the investigator has access to them at all times (GCP Article 47, Paragraph 1 Guidance Note 1). In addition, regarding case report forms, the investigator is required to retain a copy of the form submitted to the sponsor (GCP Article 47, Paragraph 1, Guidance Note 1).
In Japan, only physicians are allowed to make medical judgments, so it is considered problematic for a CRC who is not a physician to make medical judgments. Please refer to the previous opinion (2011-46).