Drug Evaluation Committee 2008-42 Necessity of Consideration of Responsible Clinical Investigator's Response to Periodic Reporting of Adverse Effects

In the case of periodic (annual) reporting of adverse reactions to the MHLW every year from the international birth date of development, the investigator should be informed in advance within 3 months after the expiration of the reporting period, and after confirming whether the clinical trial can be continued and whether the protocol and explanation and consent documents can be revised, the investigator should report to the head of the medical institution, who should ask the IRB for an opinion Do you think it is acceptable to request the IRB to hear the opinion of the head of the medical institution?

We are required to report adverse reactions to the MHLW on a regular (annual) basis every year from the date of the international birth of the development, but in between phases of a clinical trial (such as between Phase I and Phase II or between L-Phase II and Phase III), it is acceptable to summarize the information including those between phases after the next phase starts as if the development had been suspended for a long period of time. Is it acceptable to summarize and submit periodic reports including such information after the start of the next phase as in the case of a prolonged interruption of development?

Article 20, Paragraph 2 of the GCP stipulates that when the investigator becomes aware of any of the matters stipulated in Article 80-2, Paragraph 6 of the Pharmaceuticals and Medical Devices Act with regard to an investigational drug, the investigator and the head of the site must be notified of the occurrence of such matters for each investigational drug, every year from the date of first notification of the investigational plan for such investigational drug, within three months after the expiration of such period. The GCP Article 31, Article 31.2, and Article 31.3 of the GCP stipulate that the investigator and the head of the site must be notified within three months after the expiration of the clinical trial period. In addition, Article 31, Paragraph 2 of the GCP stipulates that "Upon receiving notification pursuant to Article 20, Paragraphs 2 and 3, the head of the site must obtain the opinion of the investigational review committee on the appropriateness of continuing the clinical trial at the site. The director of the investigational new drug manufacturer must follow these GCPs.

As stated in the "Reporting of Post-Marketing Adverse Reactions and Clinical Trial Adverse Reactions in Compliance with the E2B(R3) Implementation Guide," the reporting of adverse drug reaction reports is obligatory regardless of whether or not a clinical trial is conducted, unless a report is withheld by submitting a "Request for Withholding Adverse Drug Reaction/Infectious Disease Case Report" as stated in the reporting period in the "Reporting of Adverse Drug Reactions and Adverse Disease in Clinical Trials" section. As described in the "Reporting of Adverse Reactions and Adverse Drug Reactions and Infection Cases" in the "Reporting of Adverse Drug Reactions and Adverse Drug Reactions, etc.," the report must be made every year from the starting date of the mandatory reporting period (the initial submission date of the clinical trial plan notification form, or if this is not required, the start date of the implementation period described in the clinical trial protocol) in accordance with Article 273, paragraph 3 of the Enforcement Regulations of the Pharmaceuticals and Medical Devices Law.