Drug Evaluation Committee 2012-24 Preservation of Annexes/Subdivisions of Clinical Trial Protocols
Related classification: Record keeping
Initial release date: October 2012
Revised publication date: December 2021
Question
If the head of the site decides that a request for review by the Investigational Review Board (IRB) is unnecessary for the following revisions to the protocol, is it necessary for the site and the IRB office to retain the documents in question?
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(a)(2) Revision of Annexes or Subdivisions of the Clinical Trial Protocol (Addition of Other Sites)
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(b) The head of Medical Institution G shall conclude with the heads of Medical Institutions A through E respectively.Changes to an annex or a separate volume of the clinical trial protocol (changes to information specific to the site other than the site = changes to the name and location of the other site, the name and title of the principal investigator, and information on the monitors)
Our view is as follows.
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(a)(In the case of both a separate sheet and a separate volume, it must be kept at the site and IRB office.
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(b) The head of Medical Institution G shall conclude with the heads of Medical Institutions A through E respectively.In the case of a separate sheet, it must be kept at the site of the implementing medical institution and IRB office. In the case of a separate volume, neither the implementing medical institution nor the IRB office is 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 "annex" and "separate volume
- Attachment
- A document that consolidates information from all implementing medical institutions and is provided to any implementing medical institution.
- Separate volume
- Information that is specific to each implementing medical institution and prepared for individual implementing medical institutions.
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
The "separate volume" of a clinical trial protocol is defined in Article 7, Paragraph 1, Guidance 2 of the GCP as "a volume that includes the name and location of the investigational site, the name of the person to be the principal investigator, and the name of the monitor in charge of each site, when a request for a clinical trial is made to multiple sites based on a single clinical trial protocol. (2) In the case where multiple investigational sites are to be requested based on a single protocol, the name and location of the site, the name of the person who is 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 site. " The following is a summary of the information on the clinical trial implementation plan. Therefore, in cases where a study volume specific to the site is prepared, the sponsor is only required to submit to the head of the site the study volume (including revisions) pertaining to that site, and is not required to submit study volumes pertaining to other sites*1.
The head of the site is required to submit to the IRB the booklets and revisions pertaining to the site in accordance with Article 32, Paragraph 1 and Note 1 to Article 31, Paragraph 2, Guidance 3 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 site, and the head of the site is required to submit to the IRB a separate sheet of the study protocol and revisions to the relevant documents pertaining to the site.
Documents submitted to the head of the site and the IRB in accordance with the above GCP provisions must be retained for the period specified in the GCP.
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1Results of the public comment on the draft revision of the "Ministerial Ordinance on Standards for Conducting Clinical Trials on Drugs" (October 28, 2011, Evaluation and Management Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare)
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2GCP Article 31, Paragraph 2 Guidance 3
Note 1) The head of the site should ensure that the documents subject to review by the Clinical Trial Review Committee (see Article 32, Paragraph 1) are 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 promptly submitted to the Clinical Trial Review Committee and the sponsor.
Reason for revision of opinion
The opinion has been partially changed in accordance with the issuance of the GCP Guidance (August 31, 2020, Pharmaceutical Affairs Council of Japan, No. 0831-15).