Drug Evaluation Committee 2010-03 When "Records Explaining Discrepancies between Source Documents and Case Reports" is Required
Related classification: Record keeping
First published: May 2010
Question
Please tell us the Pharmaceutical Manufacturers Association of Japan's view on the cases where the so-called "record explaining discrepancies between source documents and case report forms" is required as stipulated in J-GCP.
Background
As you know, J-GCP stipulates that "Data in a case report that is based on source documents must be consistent with the source documents. If there is any kind of inconsistency with the source documents, the investigator shall prepare a record explaining the reason for the inconsistency (see below)". Although this section describes the responsibilities of the investigator, it does not specifically state what discrepancies the investigator should make a record of. As a result, the criteria for determining whether or not the sponsor should request the investigator to create records are varied in our company. As a countermeasure, we are taking measures such as stipulating the "definition of inconsistency" in the direct-reading procedure for each theme in order to eliminate the inconsistency within the same clinical trial theme, but on the other hand, since the inconsistency cannot be eliminated within the monitoring department, there have been some cases pointed out by our audit. However, we have never had any problems with GCP conformity surveys.
Question
Specifically, please give us your views on the following cases. Also, if possible, please give us your opinion on the general criteria that require the production of a "record explaining the discrepancy between the source documents and the case report". In C-3 of the "Q&A on Direct Inspection in Monitoring" prepared by the Osaka Pharmaceutical Association in March 2000, "symptoms that are not recorded in the case report form among the symptoms recorded in the nursing record" is given as an example of a specific case in which a "record explaining the discrepancy between the source documents and the case report form" should be prepared. In such cases, SDV implementation is required. In such a case, after the SDV is conducted, the following 1-3 are assumed to be the results of the monitor's inquiry to the investigator. Please explain these.
- 1.When the symptoms are added to the case report form (when the case report form is revised as it should be)
- 2.When it is confirmed that there is a reasonable explanation why the symptom is not included in the case report, but the result of such confirmation is not included in the monitoring report, etc.
- 3.When it is confirmed that the symptoms are reasonably explainable that they are not included in the case report, and the results of such confirmation are recorded in the monitoring report
(If "a record explaining the discrepancy between the source documents and the case report form" is required in case 3, it is assumed that a substantial amount of cases will be cited in reality.)
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
In the case of Question 1, the case report has been revised as it should be, so it is not necessary to prepare a record explaining the discrepancy between the original documents and the case report. However, the fact that the correction was made as a result of monitoring needs to be stated in the monitoring report. (GCP Article 22, Paragraph 2, Guidance 2)
If a third party cannot easily judge the validity of the data in the case report form from the source documents, such as when medical judgment of the investigator is added to the content of the source documents, it will be necessary to prepare a record explaining the reason for the addition. If the reason for not being included in the case report is due to general reasons from medical, pharmacological, or practical medical care, and the sponsor can explain it to a third party, it would be acceptable to include it in the monitoring report. Also, if the explanations can be provided in documents such as the protocol or case report revision manual, it is not necessary to include such explanations in the monitoring report. In regard to questions 2 and 3, we suggest that you determine the necessary response depending on which of the above applies to "can be reasonably explained".
There may be cases where the contents of the medical record prepared by the physician and the nursing record prepared by the nurse differ, so it may be useful to specify the scope of data to be handled as source documents for the clinical trial in the clinical trial protocol.