Drug Evaluation Committee 2008-10 Report of Serious Adverse Events in the Absence of a Clinical Investigator
Related classification: Adverse drug reaction reports
Initial release date: 08/2008
Revised release date: Mar 2021
Question
Background
A family member of the subject called the CRC and informed the monitor that the subject collapsed yesterday while out of the house and was transported by ambulance to another hospital, where he died and the cause of death was diagnosed as cerebral infarction.
June 9, 2008 (Monday)
The subject's attending physician was the investigator. The investigator was on an overseas business trip. The investigator called the attending physician at the destination and asked him about the situation at the time of hospitalization, the details of the treatment, and his reference opinion on the causal relationship with the investigational drug.
June 10, 2008 (Tuesday)
We asked the investigator to prepare a "Preliminary Report on Serious Adverse Events" and received it by fax.
2008.6.11 (Wednesday)
According to the protocol, the investigator must submit a detailed "Report on Serious Adverse Events" to the sponsor and the head of the site within five calendar days of learning of the SAE. However, the investigator does not return to Japan until June 18, 2008.
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1.Is the date when the sponsor received the information from the CRC or when the investigator obtained the information from the other hospital and the sponsor received the information (preliminary report) by fax? The deadline is set (if it was an adverse drug reaction).
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2.Can a subinvestigator be the reporter?
According to Article 48 of the GCP, it is the responsibility of the investigator to report the occurrence of a serious adverse event to the head of the medical institution and the sponsor. However, in the above case, if the investigator waits until the investigator returns to Japan, important safety information will not be promptly communicated. -
3.If the protocol states that the investigator is responsible for reporting serious adverse events, would it be considered a medically unavoidable deviation under GCP Article 46 if a subinvestigator were to do so on behalf of the investigator?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
Regarding the question 1.
As a source of information for the sponsor to obtain information on serious adverse events (SAEs), the medical qualification of the informant is not required. Therefore, in the case of your question, the date when the sponsor receives the information is the date when the sponsor first learns of the information, regardless of whether the source of the information is the CRC/associated investigator.
Questions about 2.
As stated in your question, it is the investigator's responsibility to report the occurrence of an SAE. However, it is unavoidable for the investigator to report the SAE to the sponsor and the head of the site, giving priority to the urgency of reporting safety information. However, it is considered necessary for the subinvestigator to provide necessary information to the investigator who is traveling overseas and appropriately confirm necessary decisions. Furthermore, it is also considered necessary for the investigator to promptly confirm the contents of the report by the subinvestigator after returning to Japan and report to the sponsor and the head of the investigational site to that effect. The discussions and confirmations between the subinvestigator and the investigator should be recorded.
Questions about 3.
We believe that this case does not fall under "a case in which the investigator did not follow the study protocol in order to avoid immediate danger to the subject or for other unavoidable medical reasons," as stipulated in Article 46, Paragraph 1 of the GCP.
In addition, Article 42 of the GCP stipulates that "The investigator must fulfill the following requirements: (1) The investigator must be able to perform the clinical trial in accordance with the protocol. （As stipulated in Article 42 of the GCP, the investigator is obliged to fulfill the responsibilities of a clinical investigator stipulated in the GCP even when traveling to academic meetings or overseas during a clinical trial. Therefore, it is considered important to fully discuss with the investigator, CRC, and sponsor what to do during such trips if the investigator is going to be in Japan or overseas during the clinical trial period.
Reason for revision of opinion
Following the issuance of the "Revision of the Q&A on Post-Marketing Adverse Reaction Reports and Clinical Trial Adverse Reaction Reports in Response to the E2B(R3) Implementation Guide" (December 9, 2020) by the Drug Evaluation and Administration Division and the Drug Safety Measures Division of the Pharmaceuticals and Life Health Bureau of the Ministry of Health, Labour and Welfare, we have revised some of the statements in the Opinion. In addition, with the enforcement of the Pharmaceutical Affairs Law (November 25, 2014), we have made minor improvements to the questions.