Drug Evaluation Committee 2012-13 Scope of Expedited Review
Related classification: Clinical Trial Review Committee
First published: Jun. 2012
Revised publication date: Apr. 2013
Question
Looking at the descriptions in GCP Article 28 and Article 31, I am not sure what is reviewed under expedited review (I have seen 2009-12, 2009-27, and 2011-43 ).
Article 28 of the GCP states that minor changes to an ongoing clinical trial can be approved through expedited review, and that minor changes are "changes that do not affect the conduct of the clinical trial, are not likely to be mentally or physically invasive to the subject, and do not increase the risk to the subject. However, the definition of "minor modification" does not fall under "when the head of the site deems it necessary (that affects the conduct of the clinical trial, may cause mental or physical harm to the subject, or increases the risk to the subject)" in Article 31 of the GCP, and there is no need to discuss it in the first place, is there? It does not need to be discussed in the first place, does it? If it falls under the category of "when the head of the site deems it necessary," then it should not be subject to expedited review, right?
If the head of the site determines that additional cases or additional investigators are not necessary, is there no problem with not requiring deliberation by the Clinical Trial Review Committee?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
In Article 31, Paragraph 2, Guidance 3 of the GCP, "When the head of the site deems it necessary" means "a change that affects the conduct of the clinical trial, has the potential to be mentally or physically invasive to the subject, or increases the risk to the subject. The definition is as follows. Therefore, "minor changes related to an ongoing clinical trial" (GCP Article 28, Paragraph 2, Guidance 2 (3) <4>), which are "changes that do not affect the conduct of the clinical trial, that are not likely to be mentally or physically invasive to subjects, and that do not increase the risk to subjects," as you mentioned in your question, are not subject to expedited It could be read as meaning that the clinical trial review committee review is not required in the first place.
However, it should be understood that the purpose of Article 31, Paragraph 2 of GCP is for the head of the site to hear the opinions of the Clinical Trial Review Committee regarding information that is important for the conduct of the clinical trial. The following items are subject to review by the Investigational Committee during the conduct of a clinical trial.
- Changes (or revisions) to the clinical trial protocol and other documents subject to review
- Serious adverse events occurring at the site
- Safety information such as serious and unpredictable adverse reactions provided by the sponsor
- Deviations or changes from the study protocol made for unavoidable medical reasons such as to avoid immediate danger to the subject
- Status of implementation of the relevant clinical trial at the site
Next, Article 28, Paragraph 2, Guidance 2 (3) <4> of GCP states that expedited review can be conducted for "minor changes related to an ongoing clinical trial" and the definition of "minor changes related to an ongoing clinical trial. Therefore, among the above-mentioned changes subject to review, "changes that do not affect the implementation of the clinical trial, are not likely to be mentally or physically invasive to the subject, and do not increase the risk to the subject" can be reviewed under expedited review.
As for the "addition of a subinvestigator," as you mentioned in your question, the review by the Clinical Trial Review Committee is required, as stated in the Guidance on Article 43, Paragraph 1 of the GCP. As for "addition of additional number of patients," as long as it is not an addition to the planned number of patients for the entire clinical trial, the review by the Clinical Trial Review Committee is basically not required.
Reason for revision of opinion
In accordance with the issuance of the GCP Guidance (December 28, 2012, Pharmaceutical Affairs Ministry, Food and Drug Administration, No. 1228/7), the explanation regarding the necessity of a review by the Clinical Trial Review Committee for additional cases has been changed.