Drug Evaluation Committee 2009-12 Positioning of "Report" in a Clinical Trial Review Committee (Part 1)
Related classification: Clinical Trial Review Committee
First published: Jul 2009
Question
An Investigator Site, where the SMO supports the Clinical Trial Office and CRC services, has been conducting expedited review for minor changes since the initial procedure. In April 2009, Investigator Site revised its SOP and added a new section called "Committee Report" in addition to the expedited review section. The contents are as follows.
The investigational review committee reports on administrative changes related to an ongoing clinical trial that has already been approved (e.g., changes in the sponsor's organization or system, changes in the name of the Investigator Site or department, changes in the investigator's title, changes in monitors) or corrections to typographical errors in the protocol (except when the corrections affect the conduct of the clinical trial). (2) The following matters may be handled as matters to be reported at the Clinical Trial Review Committee meeting. However, this does not apply to cases where the Director requests investigation and deliberation (when a Request for Investigational Review is submitted) or the Chairperson determines that investigation and deliberation are necessary, even if the case falls under reportable items.
When I inquired the reason for this to the SMO (the person in charge of the secretariat) who revised this SOP, they replied that Article 28.2.2(7)<2> (see the article below) of the GCP operation notice is the basis for the acceptable reporting response at the IRB.
The regulations should require that deviations or changes from the protocol should not be initiated prior to obtaining written approval from the investigational review committee, except when medically unavoidable, such as to avoid an immediate risk to subjects, or when the change is related to administrative matters (e.g., abbreviated).
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1.I don't think the content of Article 28.2.2 (7) <2> of the GCP operation notice is the part that stipulates IRB review and reporting, but is it the basis for what the SMO says is acceptable reporting response?
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2.I was aware that IRB reporting does not exist in GCP, but is there any problem with reporting?
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3.If the hospital's response is that a review is not required for minor changes (changes that do not affect subjects), what actions should we take as monitors?
JPMA's Opinion
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1.Article 28, Paragraph 2, Guidance 2 (7) <2> of GCP stipulates the contents of the procedure manual to be prepared by the establisher of the Investigational Review Board (hereinafter referred to as "IRB"), and it is not allowed to start a clinical trial before the IRB review gives an approval document except when it is medically unavoidable to avoid an urgent risk or the change is an administrative change. The IRB is required to establish a rule that requires the investigator not to initiate deviations or changes from the investigational protocol prior to the issuance of the approval document by the IRB review, unless the deviation or change is medically unavoidable to avoid immediate hazards or is an administrative change. In other words, it does not stipulate the scope of IRB review that is not required or the method of review, and cannot be used as a basis for accepting reporting.
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2.The contents of IRB review at the request of the Investigator Site Director can be roughly divided into two categories: "appropriateness of conducting the clinical trial" (GCP Article 30) and "appropriateness of continuing the clinical trial ("continuing review")" (GCP Article 31). There are two types of review methods: meeting review and expedited review, but the "report" review method is not indicated in GCP.
The Investigator Site Director is required to keep the documents subject to IRB review up-to-date throughout the clinical trial period, and the latest documents submitted by the sponsor are also to be submitted to the IRB. At this time, if the content of the latest document falls under Article 31 of the GCP, or if the content falls under "other cases deemed necessary by the head of the Investigator Site," as stipulated in the second paragraph of Article 31 of the GCP, the IRB must conduct a continuing review. On the other hand, there may be cases where the IRB only submits the latest documents to the IRB at the discretion of the head of the Investigator Site in response to the submission of the latest documents related to administrative changes from the sponsor, as described in your question. -
3.The content of the continuing review is stipulated in Article 31 of the GCP. Article 31, Paragraph 2, Guidance 3 of the GCP stipulates that "other changes that affect the conduct of the clinical trial, may be mentally or physically invasive to the subject, or increase the risk to the subject" and "other changes that are deemed necessary by the head of the Investigator Site. The second paragraph of Article 2, Guidance 3, of the Article 211, states that "a change that affects the conduct of a clinical trial, may cause mental or physical harm to subjects, or may increase the risk to subjects. Therefore, the head of the Investigator Site will determine the necessity of continuing review for minor changes.
If a change in a clinical trial falls under the category of a clerical change, it may be sufficient for the monitor to notify the Investigator Site of the change (or to confirm that the Investigator Site has been notified). However, in the case of a change that the sponsor thinks it would be better to obtain the opinion of the IRB from the perspective of protecting the human rights and ensuring the safety of the subject, it is necessary to confirm the decision of the head of the Investigator Site.