ICH Harmonised Tripartite Guideline E2A Flashcards
Two issues at core of ICH Harmonised Tripartite Guideline
1) the development of standard definitions & terminology for key aspects of clinical safety reporting
2) the appropriate mechanism for handling expedited (rapid) reporting in the investigational phase
Severe versus Serious
Severe–described intensity (i.e. mild, moderate, or severe). Even a minor event can be severe (i.e. severe headache)
Serious–based on patient/event outcomes. Pose a threat to patient’s life or functioning
A serious event is any untoward medical occurrence that, at any dose, . . .
—results in death
—is life-threatening (not might have caused death if more severe but actually patient was at risk of death)
—requires hospitalization or prolongs existing hospitalization
—results in disability
—congenital anomaly
unexpected adverse reaction
the nature or severity is not consistent with information in the relevant source document(s)
what determines if an AE is unexpected
—Information provided in the Investigator’s Brochure
—Reports which add significant information on specificity or severity of a known ADR (describe an event more specific or more severe than described in IB)
When is an ADR subject to expedited reporting
when it is both serious and unexpected
Events not subject to expedited reporting
—serious but expected events
—serious events not related to study product (whether expected or not)
—non-serious AEs
Examples of information that require expedited reporting
—an increase in the rate of ADRs
—lack of efficacy with a medicinal product used in treating life-threatening disease
—a major safety finding from a newly completed animal study (such as carcinogenicity)
Reporting time frame for fatal or life-threatening unexpected ADRs
—asap, but no later than 7 days after first knowledge that the case qualifies (by telephone, fax, or writing)
—complete report within 8 days
reporting time frame for serious, unexpected ADRs (not life-threatening or fatal)
asap, but no later than 15 days after first knowledge
minimum criteria for reporting ADRs (4)
an identifiable patient; a suspect medicinal product; an identifiable reporting source; and an event that can be identified as serious and unexpected with a reasonable causal relationship
how to report an ADR
CIOMS-I form is widely accepted but can be other format
should the blind be broken in the case of severe, unexpected ADRs
not necessarily. Blinding should be preserved as much as possible when possible
reactions associated with active comparator or placebo
Should be reported to the other manufacturer and/or directly to the appropriate regulatory agencies.
Events associated with placebo will usually not satisfy the criteria for an ADR and expedited reporting.
ADR that qualifies for expedited reporting in a product with more than one presentation or use
should be reported or referenced to regulatory filings across other product presentations and uses
