Drug Evaluation Committee 2013-12 Agreement record of target number of subjects
Related classification: clinical trial contracting procedures
First published: August 2013
Question
In accordance with the recent GCP revision, the "target number of subjects" has been deleted from the items to be included in the agreement (the item was also deleted from the unified form). Some sponsors may sign a separate agreement with the investigator, but if this is not done, is it unnecessary to record the target number of subjects at all?
I was under the understanding that the head of the site or the investigational review board (IRB) was checking (reviewing) whether the target number of subjects was appropriate as part of the confirmation of the investigator's requirements for conducting the clinical trial in question. For the addition of the target number of subjects, it is necessary to confirm whether the site and physicians are sufficiently prepared to accept the additional subjects (i.e., whether the increase in the number of subjects will not affect the subjects), and therefore, I believe that a change application was submitted and reviewed by the IRB. With the recent revision, since it is no longer necessary to include this information in the contract, is it correct to assume that recording the target number of subjects and IRB review is also no longer necessary? We would appreciate it if you could also provide us with some background information on why it is no longer necessary to include this information in the contract.
Opinion of the Pharmaceutical Manufacturers Association
Although the site and sponsor must agree in advance on the "target number of subjects," it is acceptable for the site and sponsor to decide whether or not records are required and how records should be kept after discussion. As a result of the discussion, there may be cases where records of letters, meetings, telephone calls, etc. between the site and the sponsor, as described in Article 41, Paragraph 1, Guidance 2 of the GCP, are kept. The "Results of the Public Comment on the Draft Ministerial Ordinance Partially Amending the Ordinance for Enforcement of the Pharmaceutical Affairs Law" (January 15, 2013, Evaluation and Management Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labor and Welfare), which was issued in conjunction with this revision, states that "the target number of subjects is one of the most frequently changed items in clinical trial agreements, and should be deleted to simplify procedures, However, this does not preclude the sponsor and the site from agreeing on the number of subjects as necessary. However, this does not preclude agreement between the sponsor and the site as necessary.
The IRB must review the ethical and scientific validity of a clinical trial, so the "target number of subjects" for the trial as a whole, as stated in the protocol, is subject to review. However, the number of subjects planned for each site in a multicenter clinical trial has not been a required item for IRB review. If the head of the site or the IRB independently considers it necessary to review the expected number of subjects only at the site in a multicenter clinical trial in deciding whether or not to conduct the clinical trial or whether or not to continue the clinical trial, the review should be conducted in accordance with a procedure that stipulates such a review. In this case, we believe that it is acceptable to conduct the review in accordance with the procedures stipulated to that effect.