ICH E2A Safety Monitoring Flashcards
(45 cards)
Adverse Event, or Adverse Experience (AE)
Any untoward (unfavorable and unintended) laboratory or clinical abnormality associated with, not necessarily caused by, the intervention.
Adverse Drug Reaction (ADR)
Any noxious and unintended response to a pre-approval stage drug given at any doses, or to a post-marketing drug given at normal doses in human.
Side Effect
SE can be both favorable and unfavorable, and thus is no longer recommended in practice due to ambiguity.
Unexpected ADR determined by Source Documents
Any adverse reaction not included in the product information from the source documents (i.e., Investigator’s Brochure of an investigational drug, or the Safety Labeling of a post-marketing drug).
Serious AE/ADR (5+1)
Any untoward medical occurrence that at any does:
- results in death,
- is life-threatening.
- requires inpatient hospitalization or prolongation of existing hospitalization
- results in persistent or signifaicant disability/incapacity, or
- is a congenital anomaly/birth defect.
- Other medical events that require intervention to prevent one of the other outcomes above.
Life-threatening Event Definition
An event in which the patient was at risk of death at the time of the event, but not in which the patient might have died hypothetically if it were more severe.
Medical Events that Require Intervention to Prevent a Serieous Events, Examples (3)
- Intensive teratment for allergic bronchospasm at ER/home
- Blood dyscrasias or convulsions that do not result in hospitalization
- Development of drug dependency or drug abuse
Severity vs Seriousness
Severity (leading event)
Seriousness (resulting outcome)
“Mild myocardial infarction (severity) did not affect survival or cardiac function (seriousness).”
Regulatory reporting obligations are defined by serious outcome, but not on severe event.
Expedited Reporting Obligations for Unexpected AE
Once an unexpected AE occurs, expedited reporting is required for additional occurrences of the AE, until source documents are amended (from unexpected to expected).
Unexpected AEs Criteria (2)
Either:
1. Not documented in Investigators’s Brochure or product Safety Label, or
2. Documented but lacks specificity or severity.
Example:
Acute renal failure / interstitial nephritis
Hepatitis / fulminant hepatitis
Expedited Reporting Requirements (2)
Both:
1. Serious, and
2. Unexpected
Ordinarily Inappropriate Circumstances for Expedited Reporting (4)
- Serious but not unexpected
- Expected but not serious
- Not serious, and not expected
- Serious AE but not related to the study
Expedited Report Source Information Examples (3)
Any one of the following:
- Spontaneous reports (for marketed drugs)
- Clinical/epidemiological investigations
- Others (registries or publications)
Valid ADR Causality Assessment
Reasonable suspected causal relationship judged by either:
- Reporting health care professional
- Sponsor
For marketed drugs, Spontaneous Reports on ADR also imply causality.
Description for Causality Examples (1+3)
Other than “cause”, the following also qualify:
- “Plausible relationship”
- “Suspected causality”
- “Causal relationship cannot be ruled out”
Degree of Causality (5)
Certainly, definitely, probably, possibly or likely related, or not related
Non-single-case for Expedited Reporting Scenarios (3)
Population based situations:
- Serious ADR, but unexpected for its rate of occurrence, which reaches over a significant clinical threshold.
- Lack of efficacy in treating life-threatening disease, posing a significant hazard to patient population.
- Major safety finding from newly completed animal studies, which translates to human.
Reporting Time Frames for Fatal or Life-threatening Unexpected ADRs
Very rapid reporting to regulatory agencies:
Initial report: ASAP but within no later than 7 calendar days, after case qualification acknowledgement by sponsor.
Complete report: within no later than 15 calendar days, after case qualification acknowledgement by sponsor (8 additional days).
Reporting Time Frames for other Serious (Non-fatal, Non-life-threatening) Unexpected ADRs
Initial report: ASAP but within no later than 15 calendar days after case qualification acknowledgement by sponsor.
Case Qualification: Minimum Criteria for Initial Report (5+1)
- An identifiable patient,
- A suspect medicinal product,
- An identifiable reporting source,
- An event or outcome identified as serious AND unexpected,
- Reasonable suspected causal relationship, and
- Other follow-up information if available.
Key Elements for Inclusion in Completed Expedited Report of Serious ADRs (6)
- Patient details
- Suspected medicinal product(s)
- Other concomitant treatment(s)
- Details of suspected ADRs
- Details on Reporter of Event
- Administrative and Sponsor details
Patient Details for Expedited Report (6)
- Initials
- Clinical investigation ID
- Gender
- Age/DOB
- Weight
- Hight
Suspected Medicinal Products(s) Details for Expedited Report (10)
Drug (3)
Usage (7)
Drug:
1. Brand name
2. International non-proprietary name (INN)
3. Batch number
Usage:
- Indications for which the drug was prescribed or tested
- Dosage form and strength
- Daily dose and regimen
- Route of administration
- Starting date and time
- Stopping date and time
- Duration of treatment
Examples of Concomitant Treatment for Expedited Report (2)
Information on the same level of details is required for concomitant treatment:
- Medicinal products (prescription and non-prescription/OTC drugs)
- Non-medicinal product therapies
