Drug Evaluation Committee 2007-37 Necessity of Review by Clinical Trial Review Committee for Extension of Subject Enrollment Period
Related classification: Clinical Trial Review Committee
First published: August 2008
Revised publication date: March 2012
Question
I would like to ask a question regarding the handling of clinical trial protocols.
The protocol for the clinical trial we are currently conducting sets a registration period for cases in addition to the clinical trial period. The protocol was revised just as the case registration period was about to expire (the contract with the medical institution is still in effect). The revisions include changes in personnel at the sponsor and CRO, and an extension of the case enrollment period.
Some medical institutions have poor case enrollment rates, and the sponsor has decided to extend the enrollment period for those institutions with high case enrollment, but not for those with low case enrollment.
We have signed a letter of agreement with the investigator and asked the IRB to discuss the matter with the medical institution that extended the case registration period, but what should we do with the medical institution that did not extend the period?
The sponsor's view is, "If the IRB is willing to discuss the case, we will revise the protocol, but we will clearly state in the request for review that the case registration period will not be extended. Or, since the sponsor is aware that the IRB will not discuss the matter, "We will only contact the investigator and the clinical trial office, and will not request IRB discussion and will not handle the matter as a required document.
However, GCP (Article 36) states that documents subject to review by the IRB must be kept up-to-date throughout the clinical trial period.
In this case, the deadline for registration of cases had passed, but the protocol had been revised, so I think it is correct that the IRB should have reviewed the protocol and kept it as an essential document.
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
The clinical trial protocol was revised due to "changes in personnel at the sponsor and CRO" and "extension of the case registration period," but the content of the revised protocol differs between medical institutions that extend the case registration period and those that do not. This is the same concept as the revision of the investigational study protocol specific to the site.
For sites that extend the case registration period, both "change of sponsor and CRO personnel" and "extension of case registration period" will be revised, and the necessary procedures must be taken according to the procedures of the site and IRB.
On the other hand, for medical institutions that do not extend the case registration period, only "changes in personnel at the sponsor and CRO" will be revised after obtaining the consent of the investigator. Even in this case, it is considered to fall under the category of "minor changes related to an ongoing clinical trial" as stipulated in GCP Article 28, Paragraph 2, Guidance 2 (3) (iv), and the procedures must be followed in accordance with the above procedure. In addition, "changes in personnel of the sponsor and CRO" from GCP Article 7, Paragraph 1, Guidance 2 can be prepared and handled as a separate volume of the clinical trial protocol. If the "change in personnel of the sponsor and CRO" does not involve the site, there is no need to submit a separate volume to all sites, and it would be acceptable to revise only for the sites that are affected by the change. Furthermore, Article 7, Paragraph 1, Guidance 3 of the GCP states, "When monitors and auditors other than those listed in the protocol or its subdivisions inspect medical records, the names of the monitors, etc., should be made available to the site. In any case, the medical institution should be able to provide the information.
In either case, the documents regarding the revision of the clinical trial protocol conducted at the relevant site must be properly stored as stipulated in Articles 34 and 41 of the GCP.
Reason for revision of opinion
In accordance with the revision (October 24, 2011) of the "Implementation of Standards for Conducting Clinical Trials on Pharmaceuticals," the explanation regarding the notation of the name, job title, and telephone number of the monitor on the clinical trial protocol has been changed.