E2: CLINICAL SAFETY DATA MANAGEMENT

Question 1

Adverse Event (or Adverse Experience) - AE

Answer 1

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Question 2

Adverse Drug Reaction (ADR)

Answer 2

All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.

Question 3

Unexpected Adverse Drug Reaction

Answer 3

An adverse reaction, 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).

Question 4

Serious Adverse Event or Adverse Drug Reaction
(SAE/ADR)

Answer 4

A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose:
* results in death,
* is life-threatening,
* requires inpatient hospitalization or prolongation of existing hospitalization,
* results in persistent or significant disability/incapacity, or
* is a congenital anomaly/birth defect.

Question 5

Severe
vs.
Serious

Answer 5

The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor medical significance (such as severe headache). This is not the same as “serious,” which is based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient’s life or functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.

Question 6

Single Cases of Serious, Unexpected ADRs

Answer 6

All adverse drug reactions (ADRs) that are both serious and unexpected are subject to expedited reporting.

Question 7

Fatal or Life-Threatening Unexpected ADRs

Answer 7

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 7 calendar days after first knowledge by the sponsor that a case qualifies, followed by as complete a report as possible within 8 additional calendar days.

Question 8

All Other Serious, Unexpected ADRs

Answer 8

Serious, unexpected reactions (ADRs) that are not fatal or life-threatening must be filed as soon as possible but no later than 15 calendar days after first knowledge by the sponsor that the case meets the minimum criteria for expedited reporting.