Drug Evaluation Committee 2021-02 Serious Adverse Events Occurring During Screening Period
Related classification: Adverse drug reaction reports
Date of first publication: Jul. 2021
Question
The protocol may stipulate that serious adverse events (SAEs) occurring in cases at the investigational site are to be collected after consent is obtained, rather than after the investigational drug administration has started.
However, I believe that events occurring during the screening period (from obtaining consent to the start of investigational drug administration) are not strictly considered "adverse events" under GCP.
In this case, although we report the event to the sponsor as an SAE in accordance with the protocol, if the site determines that the event is not an adverse event and therefore does not need to be reported to the site director or discussed by the investigational review board (IRB), is it possible to eliminate the need to take these actions?
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
Adverse events are defined in GCP Article 2, Paragraph 24 as "any disease or symptom of a disease that occurs in a subject who has received an investigational drug or post-marketing clinical trial drug. Therefore, events that occur between the time consent to participate in a clinical trial is obtained and before administration of the investigational drug are not strictly defined as "adverse events" under GCP. On the other hand, some clinical trials may conduct screening tests or washouts during this period, and the protocol may stipulate that events during this period be collected and reported as "adverse events" to ensure subject safety. In addition, the report of Working Group VI of the Council for International Organization of Medical Sciences (CIOMS), Chapter 4 "Collection and Management of Safety Data in Clinical Trials" (published in 2005), defines the point in time when the subject signs the consent form as the point in time when safety data are collected. The report states that the starting point for collecting safety data is when the subject signs the consent form, which clarifies the starting point for information collection and helps to avoid selection bias. If an event occurs that should be reported in light of the definitions and criteria stipulated in the clinical trial protocol, it would need to be reported to the head of the site and reviewed by the IRB based on the intent of Article 31, Paragraph 2 and Article 48, Paragraph 2 of the GCP.
If events occurring during the screening period (from obtaining consent to the start of administration of the investigational drug) are to be collected and reported as adverse events, as in your question, the sponsor should explain the situation to the investigator and the site prior to the start of the trial, and obtain their understanding, including how to respond.