Drug Evaluation Committee 2017-76 Definition of Adverse Events and Causal Relationship between Adverse Events and Investigational Drugs
Related classification: Adverse drug reaction reports
Initial publication date: 03/2018
Revised publication date: Mar 2021
Question
In the "Report on Serious Adverse Events" used in our hospital, the causal relationship of adverse events is a two-way choice between "undeniable" and "deniable," so unless there is a possible basis to clearly deny a causal relationship, we select "undeniable," meaning including unknown.
However, in recent years, global trials use US FDA rules, which require a decision of "no causal relationship" unless there is a clear causal relationship. We are having a hard time because there is a discrepancy between the causal relationship reported to the sponsor in the EDC and the report submitted to the Clinical Trial Review Committee. We would appreciate it if you could provide us with any good solution to this problem.
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
Normally, the evaluation criteria for the causal relationship between an investigational drug and an adverse event are stipulated in the protocol and other documents provided by the sponsor to the investigational sites. Therefore, investigators are required to evaluate the causal relationship based on the criteria stipulated in the protocol.
However, the causal relationship is an important piece of information that is involved in the decision whether or not to report to the regulatory authorities, etc. Therefore, when reporting the same event to the sponsor and the head of the investigational site, the causal relationship evaluated according to different standards should not be reported. Therefore, it is not desirable to report the same event to the sponsor and the head of the site based on different criteria. Therefore, it is desirable to report the causal relationship evaluated in accordance with the criteria in the study protocol when reporting to the head of the site.
Please note that Guidance 18 (10) of GCP Article 2 defines an adverse effect as a causal relationship between an investigational drug and an adverse event that has at least a reasonable relationship and for which a causal relationship cannot be ruled out.
Reason for revision of opinion
With the issuance of the GCP Guidance (No. 0831-15 issued by the Pharmaceutical Affairs Agency on August 31, 2020), minor changes have been made to the description.