CLINICAL SAFETY DATA MANAGEMENT: DEFINITIONS AND STANDARDS FOR EXPEDITED REPORTING ICH Harmonised Tripartite Guideline

Question 1

There are two issues within the broad subject of clinical safety data management that are appropriate for harmonization at this time:

Answer 1

(1) the development of standard definitions and terminology for key aspects of
clinical safety reporting, and
(2) the appropriate mechanism for handling expedited (rapid) reporting, in the
investigational (i.e., pre-approval) phase.

Question 2

When doing expedited reporting what should be reported?

Answer 2

Single Cases of Serious, Unexpected ADRs

This applies to reports from spontaneous sources
and from any type of clinical or epidemiological investigation, independent of
design or purpose. It also applies to cases not reported directly to a sponsor or
manufacturer (for example, those found in regulatory authority-generated ADR
registries or in publications). The source of a report (investigation, spontaneous,
other) should always be specified.

Question 3

There are situations in addition to single case reports of “serious” adverse events
or reactions that may necessitate rapid communication to regulatory authorities;
appropriate medical and scientific judgement should be applied for each
situation. In general, information that might materially influence the benefitrisk assessment of a medicinal product or that would be sufficient to consider
changes in medicinal product administration or in the overall conduct of a clinical
investigation represents such situations. Examples include:

Answer 3

a. For an “expected,” serious ADR, an increase in the rate of occurrence which is
judged to be clinically important.
b. A significant hazard to the patient population, such as lack of efficacy with a
medicinal product used in treating life-threatening disease.
c. A major safety finding from a newly completed animal study (such as
carcinogenicity).

Question 4

Reporting Time Frames
1. Fatal or Life-Threatening Unexpected ADRs
Certain ADRs may be sufficiently alarming so as to require very rapid
notification to regulators in countries where the medicinal product or indication, formulation, or population for the medicinal product are still not approved for marketing, because such reports may lead to consideration of suspension of, or other limitations to, a clinical investigations program. Fatal or life-threatening,
unexpected ADRs occurring in clinical investigations qualify for very rapid reporting. Regulatory agencies should be notified (e.g., by telephone, facsimile transmission, or in writing) as soon as possible but no later than __________ after first knowledge by the sponsor that a case qualifies, followed by as complete a report as possible within ________. This report must include an assessment of the importance and implication of the findings, including relevant previous experience with the same or similar medicinal products.

Answer 4

7 calendar days

within 8 additional calendar days

Question 5

2. All Other Serious, Unexpected ADRs
   Serious, unexpected reactions (ADRs) that are not fatal or life-threatening must
   be filed as soon as possible but no later than ________ after first
   knowledge by the sponsor that the case meets the minimum criteria for expedited
   reporting.

Answer 5

15 calendar days

Question 6

3. Minimum criteria for reporting
   Information for final description and evaluation of a case report may not be
   available within the required time frames for reporting outlined above.
   Nevertheless, for regulatory purposes, initial reports should be submitted within
   the prescribed time as long as the following minimum criteria are met:

Answer 6

an
identifiable patient; a suspect medicinal product; an identifiable reporting source;
and an event or outcome that can be identified as serious and unexpected, and for
which, in clinical investigation cases, there is a reasonable suspected causal
relationship. Follow-up information should be actively sought and submitted as
it becomes available

Question 7

How do you report expedited adverse event reporting

Answer 7

CIOMSI-I form

Question 8

What are the key DATA ELEMENTS FOR INCLUSION IN EXPEDITED
REPORTS OF SERIOUS ADVERSE DRUG REACTIONS

Answer 8

1. Patient Details
2. Suspected Medicinal Product(s)
3. Other Treatment(s)
4. Details of Suspected Adverse Drug Reaction(s) then outcome
5. Details on Reporter of Event (Suspected ADR)
6. Administrative and Sponsor/Company Details