Drug Evaluation Committee 2017-52 Prior Agreement and Approval for Deviations from the Clinical Trial Protocol
Related classification: Deviation
Date first published: December 2017
Question
GCP Article 46 Guidance 1 includes the following statement
"The investigator or subinvestigator shall not deviate from or modify the study protocol without prior written agreement with the sponsor and prior written approval from the investigational review committee."
Regarding the above, if a deviation is known in advance, does this mean that prior agreement with the sponsor and review by the investigational review committee are required for the details of the deviation? For example, if the subject is unable to come to the hospital during long vacations such as New Year holidays or Golden Week vacations, and the deviation is known in advance, I think this would be applicable. My personal opinion is that it means that deviation from the protocol is not allowed in the first place, and that the subject must not implement the contents of the protocol revised before the agreement and the approval of the investigational review committee. However, I was told that it means that others must make an agreement with the sponsor in advance before deviating from the plan and that the Clinical Trial Review Committee will review the agreement.
If the agreement and the review by the Trial Review Committee are required in advance, what kind of measures and forms should be used to review them? Also, if we do that, does it not constitute a deviation?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
If a deviation from the protocol is known in advance, the investigator must report it to the sponsor and discuss the appropriateness of the deviation and its impact on the conduct of the trial from the perspective of ensuring the safety of the subjects. If the discussions lead to the conclusion that it is appropriate to revise the protocol, the clinical trial will be conducted based on the revised protocol after obtaining approval from the Clinical Trial Review Committee in accordance with the usual procedures. However, if the protocol is not revised, the action taken in accordance with GCP Article 46 will constitute a deviation from the protocol.
GCP Article 46 and its guidance indicate that the clinical trial must be conducted in accordance with the protocol, and stipulate exceptional responses in cases where the protocol is not followed for compelling medical reasons, such as to avoid immediate danger to the subject.