Why do we need to report safety issues?
To gain knowledge of the safety of the IP in humans and meet regulatory requirements
Why do we need to report safety issues?
To improve study design or procedures if needed
Why do we need to report safety issues?
To keep study participants informed of risks
Why do we need to report safety issues?
To comply with ICH GCP
Why do we need to report safety issues?
To gain an overall understanding of the safety of an IP before it is released to market
Definition of an Adverse Event (AE)
Untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does NOT necessarily have a causal relationship with treatment.
Definition of Untoward in context of AE
any unfavorable or unintended sign or disease temporally associated with the use of IP whether or not related to IP.
Is a Pre existing Medical Condition noted in medical history an AE?
no
If a pre-existing medical condition worsens (increases in frequency or intensity) is this an AE?
yes
Are scheduled procedures an AE?
No
Are procedures that are newly scheduled due to a condition an AE?
yes
Are elective surgeries planned prior to enrollment an AE?
no
Are out of range lab results that are not clinically significant (NCS) an AE?
no
For an AE to be an SAE, it has to fulfill one of these 6 criteria
- Results in death
- is life threatening
- results in hospitalization or prolonged existing hospitalization
- results in persistent or significant disability/incapacity
- results in a congenital anomaly or birth defect
- considered a significant medical event (PI judgetment)
Definition of SAE criteria: (1) results in death or (2) is life threatening
An event in which subject died (any cause of death) or was at risk of death at the time of event.
Does not refer to an event that hypothetically caused death if it was more severe
Definition of SAE criteria: An event that results in hospitalization or prolonged hospitalization
Hospitalization is not defined in ICH but this should be defined in the protocol. (ex: overnight stay, admission to hospital, 24h stay etc.) Does not refer to elective surgery.
Definition of SAE criteria: Results in persistent or significant disability
Substantial disruption or change from baseline of a person’s ability to conduct normal life functions (ex: loss of vision, loss of mobility, loss of cognition)
Definition of SAE criteria: Is a congenital anomaly/birth defect
Any anatomic or functional abnormalities, (including metabolic disorders) present in the time of birth of an infant exposed during the pregnancy to the test drug
Protocol defines exposure to drug for a female subject, a male subject and timelines for pregnancy reporting after completion of study
Definition of SAE criteria: Is a congenital anomaly/birth defect
Any anatomic or functional abnormalities, (including metabolic disorders) present in the time of birth of an infant exposed during the pregnancy to the test drug
Protocol defines exposure to drug for a female subject, a male subject and timelines for pregnancy reporting after completion of study
Definition of SAE criteria: Considered a significant medical event
Based on PI Judgement - May jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed previously
Adverse Events of Special Interest (AESI)
Protocol may define other events of special interest that are potentially associated with investigational compound or disease under study.
(May be serious or non serious) but are of scientific and medical concern specific to the sponsor’s product or study, for which ongoing monitoring and rapid communication by the PI to sponsor is needed
Other Expedited Safety Reporting
other events that do not fulfill SAE criteria but require immediate reporting for the safety evaluation of the drug. Ex:
○ Pregnancy
○ Drug overdose
○ Drug misuse
○ Drug dependency
Study endpoint AE
special type of adverse event that refers to outcomes measured to evaluate efficacy of tested product
- Evaluates effect of a drug on disease related mortality or morbidity
- Check protocol for reporting requirements
Description of AE should contain: (6)
Term/Diagnosis
Start/stop date
severity and seriousness
Causality
Actions Taken
Status, follow up and outcome
