Drug Evaluation Committee 2018-18 Starting Date for Receipt of SAE Report by Clinical Trial Sponsor
Related classification: Adverse drug reaction reports
Initial publication date: 08/2018
Revised publication date: Mar 2021
Question
We have a question regarding Day 0 for the occurrence of serious adverse events ("SAEs") in global clinical trials. I think it has been conventionally recognized that when an SAE occurs in Japan, Day 0 is when the investigator contacts the sponsor (including the CRO monitor) and the clock starts ticking. In the case of a global clinical trial where an SAE is reported by EDC and safety evaluation and processing is performed by the sponsor's overseas Pharmacovigilance department (hereinafter referred to as the sponsor's overseas PV department), I feel that the question is at what point Day 0 should be considered. From a conventional Japanese perspective, Day 0 could be the date in Japan time when the Japanese investigator enters the data into the EDC and submits it. However, if we assume that Day 0 is when the sponsor's overseas PV department sees the report (i.e., even if the report is sent before the start of work, it is not counted), it may already be Day 1 in Japan at that time due to the time difference.
I believe that SAEs that occurred at the Japanese site should be reported on 7/15 in accordance with the Japan time day count, but the sponsor considers the time when the overseas PV department receives the report as Day 0 (it is unclear whether this is during business hours or not). In such a case, what date should be considered as Day 0? Also, if we assume that Day 0 is the date of receipt by the sponsor's overseas PV department (e.g., June 30), then Day 0 in Japan would also be June 30 (even though it is already July 1), and if it is subject to urgent reporting, would it have to be reported to the authorities by July 7 or July 15? Is this correct?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
For global clinical trials where information is obtained through EDC, the starting date for the sponsor to report adverse reactions to the regulatory authority (e.g., handling of time differences) is determined based on the company's own information collection process, and is considered to be different for each company.
However, in the case of information from outside Japan, the reporting deadline should be set based on the date the information was obtained in Japan, not the local time of the primary source of information (see "E2B(R)"). (3) Postmarketing Adverse Reaction Reports and Clinical Trial Adverse Reaction Reports in Response to the Implementation Guide," NHI Drugs and Medicines Agency Announcement No. 0331-6, NHI Drug Safety Agency Announcement No. 0331-1, March 31, 2009, Attachment 4 (1).
As one example of handling based on this, when a serious adverse event is reported directly from the site to the sponsor's overseas PV department via EDC, the date of acquisition in Japan is 0. For example, if the overseas acquisition date is June 30 and the domestic acquisition date is July 1 due to the time difference, July 1 will be Day 0.
When the in-country caretaker reports adverse reactions to the study drug, the date when either the foreign sponsor or the in-country caretaker first obtained the information is considered as the date when the information was obtained (see "Revision of Q&A on Post-Marketing Adverse Reaction Reports and Adverse Reaction Reports in Response to the E2B(R3) Implementation Guide"). (Attachment: July 10, 2027, Ministry of Health, Labour and Welfare, Pharmaceuticals and Consumer Health Bureau, Drug Evaluation and Control Division and Drug Safety Division, Office Communication Q50).
Reason for revision of opinion
In accordance with the issuance of "Revision of Q&A on Post-Marketing Adverse Reaction Reports and Clinical Trial Adverse Reaction Reports in Response to the E2B(R3) Implementation Guide" (July 10, 2028, Ministry of Health, Labour and Welfare, Pharmaceuticals and Welfare Bureau, Drug Evaluation and Administration Division and Drug Safety Division, Office Communication Q50), minor changes were made in the descriptions.