ICH E2A Definitions and Standards for Expedited Reporting Flashcards
University of Cali slideshow
Define Adverse Event
An untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a casual relationship with this treatment.
An ____________ can be any unfavorable and unintended sign (e.g. an abnormal lab finding), symptom, or disease temporarily associated with the use of a drug, without any judgment about causality or relationship to the drug.
adverse event
Define Serious Adverse Event
death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Hospitalization
Admission to the hospital for longer than 24 hours or prolongation of hospital stay due to adverse event
Congenital Anomaly
Exposure to a medical product prior to conception or during pregnancy resulting in an adverse outcome in the child.
Example: Thalidomide - babies born with deformed arms and legs
Important medical events that may not result in death, be life threatening, or require hospitalization may be considered a ____________________ when based upon appropriate medical judgment (they may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition)
serious adverse event
Toxicities from the study drug are consdiered expected (vs unexpected) if found in…
- safety info on approved products is reflected in product labeling (package insert)
- up to date safety info on the products under investigation is found in the Investigator’s Brochure
- from these sources the protocol and ICF is written to explain and describe what risks we currently expect from this study drug
- safety profile of other drugs in this same class
Define an Unexpected Adverse Event
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in the investigator brochure or is not listed at the specificity or severity that has been observed; or, if an investigator brochure is not required, available, is not consistent with the risk info described in the general investigational plan or elsewhere in the current application, as amended.
The following are examples of ________________
- hepatic necrosis would be unexpected (by virtue of greater severity) if the investigator brochure only referred to elevated hepatic enzymes or helpatitis
- cerbral thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) if the IB only listed cerebral vascular accidents
Unexpected Adverse Events
Severity vs Serious
Severity: Refers to the intensity of the event. Is expressed in ‘grades’ of severity. Event itself may be minor (severe headache)
Serious: events that threaten subjects life or functioning
It is the reponsibility of the ___________ to concur with all intensity assessments added to the database for the events identified in the subject
Principal Investigator
Adverse Drug Reaction
All noxious and unintended responses to medicinal product related to any dose should be considered adverse drug reactions.
“responses to medicinal products” means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e. the relationship cannot be ruled out
Unexpected Adverse Drug Reaction
An adverse reaction which the nature or severity of which is not consistent with the applicable product information (e.g. Investigator’s Brochure for an unapproved investigational medicinal product)
life threatening
RISK OF DEATH AT THE TIME OF THE EVENT
-It does not refer to an event which hypothetically might have caused death if it were more severe.
Standards for Expedited Reporting: AE must be
- Serious
- Unexpected
- Related (reasonable suspected causal relationship to IP)
Reporting Timeframes for Fatal or Life-Threatening Unexpected ADR’s
-REGULATORY AUTHORITIES should be notified by SPONSOR in writing soon as possible but no later than 7 calendar days after first knowledge by the sponsor
-followed by as complete report within 8 additional calendar days
Reporting Time Frame for All Other Serious, Unexpected ADRs
as soon as possible but no later than 15 calendar days after first knowledge by the SPONSOR to REGULATORY AUTHORITIES
Breaking the blind
1) When should it occur?
2) Who should do it?
1) when a serious adverse reaction is judged reportable on an expedited basis
2) only broken for that specific patient by the sponsor
What is the timeline for reporting serious, Fatal or Life-Threatening Unexpected ADRs ?
-7 calendar days from the day it became known for the first time
-Additional 8 days for follow up report
Sponsor reports to regulatory authorities
What is the timeline for all other Serious, Unexpected ADRs?
15 calendar days from the day it became known for the first time
Sponsor reports to regulatory authorities
What does severity refer to?
the intensity of a condition
like a mild, moderate, or severe headache
A severe headache can be considered NOT serious when it does not comply with the conditions of resulting in death, being life threatening, requiring inpatient hospitalization or prolongation of existing hospitalization, resulting in persistant or significant disability/incapacity or a congenital anomaly/birth defect
Minimum Criteria for Reporting
Identifiable patient, name of IP, identifiable reporting source, event or outcome that is serious and unexpected, reasonable causal relationship to IP
Hospitalization
Admission to the hospital for longer than 24 hours or prolongation of hhospital stay due to adverse event
Disability
A substantial disruption of a person’s ability to conduct normal life funtions.
Examples: loss of speech, fatigue so great the subject cannot get out of bed at all, loss of memory, paralysis
Congenital Anomaly
Exposure to a medical product prior to conception or during pregnancy resulting in an adverse outcome in the child.
Example: Thalidomide - babies born with deformed arms and legs
Define an Unexpected Adverse Event
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in the investigator brochure or is not listed at the specificity or seerity that has been observed; or, if an investigator brochure is not required, available, is not consistent with the risk info described in the general investigational plan or elsewhere in the current application, as amended.
Severity (vs Serious)
Refers to the intesity of the event and can be used with any even without regard to whether or not it meets the federal criteria for “serious”… is expressed in ‘grades’ of severity
Investigator safety reporting responsibilities
-All serious adverse events (SAEs) should be reported immediately to the sponsor
-Also comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious adverse drug reactions to the regulatory authority(ies) and the IRB/IEC.
Safety Events:
Investigators report to the sponsor:
Any adverse event (AE) determined to be caused by (or probably caused by) the drug
Safety Events:
Sponsors report to investigators and and regulatory authorities
Any ADR that is both serious and unexpected
Sponsors should also inform investigators of any new observations regarding the drug, especially AEs and safe use concerns
Safety Events:
Investigators and sponsors report to the IRB
All unanticipated problems (UAPs) involving risks to human subjects or others
