Drug Evaluation Committee 2012-24 Preservation of Appendixes/Subdivisions of Clinical Trial Protocols
Related classification: Record keeping
First published: October 2012
Revised publication date: December 2021
Question
If the Chairperson of an Investigator Site decides that a request for review by the Investigational Review Board (hereinafter referred to as "IRB") is unnecessary for the following revisions to the protocol, is it necessary for the Investigator Site and the IRB office to retain the relevant documents?
-
(A)(2) Revision of Annexes or Subdivisions of the Clinical Trial Protocol (Addition of Other Investigator Sites)
-
(b)Changes to annexes or sub-booklets of the clinical trial protocol (changes to information specific to Investigator Sites other than the relevant Investigator Site = changes to the name and location of the other Investigator Site, the name and title of the principal investigator, and the information on monitors)
Our view is as follows.
-
(A)(In the case of both a separate sheet and a separate volume, it must be kept at the Investigator Site and the IRB office.
-
(b)In the case of a separate sheet, it must be kept at the Investigator Site and IRB office. In the case of a separate document, both the Investigator Site and the IRB office are not required to retain the information.
Based on past Clinical Trial 119 opinions, there is a difference of opinion within the company, with some saying that both (a) and (b) do not require retention at the IRB office. We are aware of the distinction between "annexes" and "separate volumes" as follows, but we would appreciate it if you could also point out any errors.
Distinction between "Appendix" and "Separate volume
- Separate sheet
- A document that consolidates information from all Investigator Sites and is provided to any Investigator Site.
- Separate volume
- Information that is specific to each Investigator Site and prepared for each individual Investigator Site.
JPMA's Opinion
Regarding the separate volume of the protocol, Article 7, Paragraph 1, Guidance 2 of the GCP states, "When a request for a clinical trial is made to multiple Investigator Sites based on a single protocol, the name and location of each site, the name of the person to be the principal investigator, and the name of the monitor in charge of each site (in the case of multiple monitors, the name of the monitor in charge of each site) must be clearly indicated in the protocol. (2) In the case where multiple investigator sites are to be requested based on a single protocol, the name and location of the site, the name of the person to be the principal investigator, and the name and telephone number of the monitor (or the representative if there are multiple monitors) in charge of each site may be submitted as a separate volume of the protocol as information specific to each site, and only that volume pertaining to that site may be submitted to the director of each Investigator Site. " The following is a summary of the information on the clinical trial implementation plan. Therefore, in cases where a booklet specific to the Investigator Site has been prepared, the sponsor is only required to submit the booklets (including revisions) pertaining to that Investigator Site to the head of the Investigator Site, and is not required to submit booklets pertaining to other Investigator Sites*1.
The head of the Investigator Site is required to submit to the IRB the booklets and revisions pertaining to the Investigator Site in accordance with Article 32.1 and Note 1*2 of Guidance 3 of Article 31.2 of the GCP.
On the other hand, GCP does not have an "Appendix to the Clinical Trial Protocol," as you asked, but it should be handled in accordance with the above GCP provisions. In other words, the sponsor is required to submit to the head of the Investigator Site, and the head of the Investigator Site is required to submit to the IRB a separate sheet of the study protocol and revisions to the relevant documents pertaining to the Investigator Site.
Documents submitted to the Investigator Site Director and IRB in accordance with the above GCP provisions must be retained for the period specified in the GCP.
-
1Results of the public comment on the draft revision of the "Ministerial Ordinance on Standards for Conducting Clinical Trials on Drugs" (October 28, 2011, Ministry of Health, Labour and Welfare, Evaluation and Management Division, Pharmaceutical and Food Safety Bureau)
-
2GCP Article 31, Paragraph 2 Guidance 3
Note 1) The Chairperson of the Investigator Site shall keep the documents subject to review by the Clinical Trial Review Committee (see Article 32, Paragraph 1) up to date throughout the clinical trial period. When additional, updated or revised such documents are submitted by the sponsor, all such documents shall be promptly submitted to the Clinical Trial Review Committee and the investigator, and when additional, updated or revised such documents are submitted by the investigator, all such documents shall be submitted to the Clinical Trial Review Committee and the sponsor.
Reason for revision
We have partially changed the opinion text in accordance with the issuance of the GCP Guidance (August 31, 2020, Pharmaceutical Affairs Council of Japan, No. 0831-15).