AE & SAE

Question 1

For behavioral trials that do not involve treatment with a drug, an
AE may be defined as:

Answer 1

Any unfavorable, unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome, or disease that occurs during the study, having been absent at baseline, or if present at baseline appears to worsen.

Question 2

Determining whether an incident is a reportable AE—and if so, what should be reported about it, to whom, and when—depends on
many factors, including:

Answer 2

Previous experience and knowledge of the drug or intervention,
The disease being treated, and
Regulatory requirements.

Question 3

Not all AEs require reporting, as they might not directly impact participant risk or present significant new
findings.

Answer 3

Requirements for the
reporting of AEs are defined in each protocol.

Question 4

What must an investigator do with SAE reporting?

Answer 4

The investigator must report all Serious Adverse Events to the sponsor immediately. The immediate reports
should be followed promptly by detailed, written reports.
In the event of a death, the investigator should supply the sponsor and the IRB with any additional requested
information.

Question 5

For IND studies FDA guidelines (21 CFR 312.32) require expedited reporting by the sponsor of all AEs that
are associated with the use of the drug, serious, unexpected, and reasonably related to the investigational
product.

Answer 5

Related and unexpected fatal or life-threatening AEs (severity grade 4 or 5) that are associated with the
use of the drug must be reported to FDA by telephone or fax no later than 7 calendar days after the
sponsor first learns of the event. This initial report must be followed within 8 additional calendar days by
a written safety report that is as complete as possible.
FDA must be notified of serious, related, and unexpected AEs associated with the use of the drug that
are not fatal or life-threatening in a written safety report no later than 15 calendar days after the
sponsor first learns of the event.
The sponsor should report pertinent follow-up information for previously submitted reports to the FDA
as soon as it is available, including for AEs that were not initially deemed reportable if the follow-up
information causes a change in the assessment.

Question 6

Adverse event reporting.

Answer 6

Federal regulations (45 CFR Part 46, Subpart A) require
written procedures and policies for ensuring that “unanticipated problems” involving risks to participants are
reported to the IRB, appropriate institutional officials, and the relevant department or agency head.

Question 7

All SAEs should be followed until resolution, or until the condition has stabilized with no further change
expected.

Answer 7

According to FDA guidance, participants should receive appropriate medical evaluation and
treatment until the resolution of any emergent condition related to the study intervention that develops during
or after the course of their participation in a study, even if the follow-up period extends beyond the end of
the study.
When a participant discontinues participation in a study because of an SAE, investigators should:
Continue to follow up on the SAE as noted above.
Document the SAE and its follow-up in the participant’s record.
Attempt to complete any final evaluations required by the study protocol.
Attempt to perform other medical evaluations to try to determine the cause of the SAE and its possible
relationship to the study intervention. These evaluations would include obtaining an autopsy report, if
available, in the event of a participant’s death.