Safety Reporting

Question 1

Why do we need to report safety issues?

Answer 1

To gain knowledge of the safety of the IP in humans and meet regulatory requirements

Question 2

Why do we need to report safety issues?

Answer 2

To improve study design or procedures if needed

Question 3

Why do we need to report safety issues?

Answer 3

To keep study participants informed of risks

Question 4

Why do we need to report safety issues?

Answer 4

To comply with ICH GCP

Question 5

Why do we need to report safety issues?

Answer 5

To gain an overall understanding of the safety of an IP before it is released to market

Question 6

Definition of an Adverse Event (AE)

Answer 6

Untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does NOT necessarily have a causal relationship with treatment.

Question 7

Definition of Untoward in context of AE

Answer 7

any unfavorable or unintended sign or disease temporally associated with the use of IP whether or not related to IP.

Question 8

Is a Pre existing Medical Condition noted in medical history an AE?

Answer 8

no

Question 9

If a pre-existing medical condition worsens (increases in frequency or intensity) is this an AE?

Answer 9

yes

Question 10

Are scheduled procedures an AE?

Answer 10

No

Question 11

Are procedures that are newly scheduled due to a condition an AE?

Answer 11

yes

Question 12

Are elective surgeries planned prior to enrollment an AE?

Answer 12

no

Question 13

Are out of range lab results that are not clinically significant (NCS) an AE?

Answer 13

no

Question 14

For an AE to be an SAE, it has to fulfill one of these 6 criteria

Answer 14

1. Results in death
2. is life threatening
3. results in hospitalization or prolonged existing hospitalization
4. results in persistent or significant disability/incapacity
5. results in a congenital anomaly or birth defect
6. considered a significant medical event (PI judgetment)

Question 15

Definition of SAE criteria: (1) results in death or (2) is life threatening

Answer 15

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

Question 16

Definition of SAE criteria: An event that results in hospitalization or prolonged hospitalization

Answer 16

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.

Question 17

Definition of SAE criteria: Results in persistent or significant disability

Answer 17

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)

Question 18

Definition of SAE criteria: Is a congenital anomaly/birth defect

Answer 18

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

Question 19

Definition of SAE criteria: Is a congenital anomaly/birth defect

Answer 19

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

Question 20

Definition of SAE criteria: Considered a significant medical event

Answer 20

Based on PI Judgement - May jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed previously

Question 21

Adverse Events of Special Interest (AESI)

Answer 21

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

Question 22

Other Expedited Safety Reporting

Answer 22

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

Question 23

Study endpoint AE

Answer 23

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

Question 24

Description of AE should contain: (6)

Answer 24

Term/Diagnosis
Start/stop date
severity and seriousness
Causality
Actions Taken
Status, follow up and outcome

Question 25

Definition of Severity

Answer 25

The intensity of the AE ( mild, moderate, severe or follow CTCAE ratings)
Severity ≠ Seriousness

Question 26

Causality

Answer 26

relatedness to study treatment as defined by protocol:
ex: not related, unlikely related, possibly related, probably related, definitely related,

Question 27

SUSAR

Answer 27

Suspected Unexpected Serious Adverse [Drug] Reaction
Potentially related to study drug

All are reported in 24h to Sponsor

-Fatal life threatening SUSAR: reports due in 7 days to RA/EC/IRB
-Non Fatal life threatening SUSAR: reports due in 15 days to RA/EC/IRB

Question 28

Adverse Drug Reaction

Answer 28

causal relationship with medicinal product
not all ADRs are SUSARs but all SUSARs are ADRs/serious

Question 29

SUSAR Information Distribution

Answer 29

Sponsors are required to notify investigators about all new emerging safety info (SUSARs) related to IMP.
Investigators required to stay informed about emerging safety info

Question 30

Pharmacovigilance Safety Information Processing

Answer 30

Sponsor pharmacovigilance team must analyze safety event information and update the ICF if this new information impacts patients willingness to participate. In some exceptional emergency cases, a verbal re-consent can occur.

Question 31

IP Authorization and Safety Information

Answer 31

Information goes into a safety database. Information goes into drug registration package. Safety information is in the patient information pamphlet.

Question 32

CRA Responsibility in Safety Reporting

Answer 32

Must be familiar with safety reporting, all definitions and protocol to conduct site staff trainings:
SIV: reporting requirements, investigator’s responsibility, sections of the IB with AE info, subject identity protection during reporting
IMV: new investigator joins, site fails to follow requirements and re-training is required
COV: follow up on safety issues if applicable

Determine all AEs are appropriately reported (completeness, accuracy, timelines, review source for unreported events, check IRB was informed accordingly)

Support and guide site in safety issues

Ensure site is informed about all new safety issues and PIs confirm acknowledgement

Question 33

Definition: Safety Notifications

Answer 33

new relevant safety information about the investigational product that has not been included in the last version of the IB:
- individual SUSARs
- periodic SUSAR summaries
- SUSAR line listings which need to be acknowledged