Drug Evaluation Committee 2012-23 Matters to be included in explanatory documents for test subjects and their scope
Related classification: Other
First published: Sep. 2012
Question
Please tell me two points regarding the items to be included in the consent document and the scope of such items.
Question 1: Information on side effects in the consent document
Is it necessary to include information on side effects in phase I? Also, what guidelines or regulations, if any, are used as the basis for this information?
In many cases, a draft prepared by the sponsor is provided to the investigator before the investigator prepares the consent document, but the sponsor may or may not include phase I data. The GCP Article 51 also does not specify the details.
Except in special cases, such as when the results are unique to the investigational drug and have an impact on the Phase II and III study protocols, etc., the doses and subjects are significantly different from those in the Phase II and III studies, and it is difficult for subjects to refer to the information and is not only meaningless but also unnecessarily increases their anxiety. Therefore, I would like to prepare a consent explanation document without including such information if it is not required.
Question 2: Sample collection volume
I don't think there is any regulation in GCP that says "the amount of specimen to be collected should be specified. I don't think there is any regulation that says "the amount of specimen to be collected should be specified" under GCP, but is there any guideline or regulation that provides a basis for this?
When we asked the sponsor, they responded in the same way as above, "It is safer to state the amount of specimens to be collected, so we would like you to leave it as it is.
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
Question 1.
In Article 51, Paragraph 1, Guidance 2 of GCP, regarding matters to be described in the explanatory document for subjects, "Item 5, 'the anticipated benefits of the investigational drug on the subject's mental and physical health (if such benefits are not expected, a statement to that effect) and the anticipated disadvantages to the subject' refers to the anticipated clinical benefits and risks or disadvantages to the subject. The "anticipated benefits to the subject's physical and mental health (if no such benefits are anticipated) and anticipated disadvantages to the subject" refers to anticipated clinical benefits and risks or inconveniences. （The "expected clinical benefit" refers to the expected clinical benefit and the "expected risk or inconvenience" (see below). We believe that this balance of benefits and risks associated with participation in a clinical trial is important information in making a decision to participate in a clinical trial.
Therefore, the "anticipated risks" to be described in the subject information document should be discussed after the sponsor evaluates the clinical data and other information collected up to that point and presents the most recent safety profile of the study drug to the investigator. There is no notice or guidance that states that information on adverse reactions in Phase I trials must be included in the instructions to subjects. For Phase II trials that are conducted for the first time after a Phase I trial, information from the Phase I trial is useful. For trials initiated after that, it is recommended that the need for adverse effect information from Phase I trials be appropriately determined from the perspective of the benefit-risk balance of clinical trial participation based on the information obtained.
Question 2.
Article 51, Paragraph 1, Guidance 1 (5) of the GCP stipulates "anticipated clinical benefits and risks or inconveniences" as items to be described in the explanatory document for subjects. In ICH-GCP, the following items are listed as items that should be included in the explanatory document for subjects.
4.8.10 (d) The trial procedures to be followed, including all invasive procedures.
4.8.10 (d) The trial procedures to be followed, including all invasive procedures.
There is no notice or guidance that states that the number and volume of blood and urine samples must be included in the instructions to subjects. However, since these are clinical trial procedures that involve anticipated inconvenience or invasiveness in participating in a clinical trial, it is desirable to provide sufficient explanation from the standpoint of the subject, taking into consideration the burden on the subject and his/her anxiety about participating in a clinical trial.