Adverse Events

Forms

Adverse event reporting is a primary obligation of the Investigator. The Research Ethics Board has an obligation to ensure the safety of the study participants. Monitoring safety related issues are a key component of that responsibility. In order for the REB to fulfill its mandate, the following will help guide safety reporting to Canadian SHIELD Ethics Review Board:

Regulatory Guidance  : (ICH GCP sections 3.3.8 and 4.11)

• The investigator should promptly report unexpected serious adverse drug reactions (serious ADR’s),

• Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects,

• New information that may affect adversely the safety of the subjects or the conduct of the trial

Definitions : (ICH Safety Reporting E2A)

“Unexpected Adverse Drug Reaction”

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). (See section 3.C.)

B. Serious Adverse Event or Adverse Drug Reaction

During clinical investigations, adverse events may occur which, if suspected to be medicinal product-related (adverse drug reactions), might be significant enough to lead to important changes in the way the medicinal product is developed (e.g., change in dose, population, needed monitoring, consent forms). This is particularly true for reactions, which, in their most severe forms, threaten life or function. Such reactions should be reported promptly to regulators. Therefore, special medical or administrative criteria are needed to define reactions that, either due to their nature (“serious”) or due to the significant, unexpected information they provide, justify expedited reporting. To ensure no confusion or misunderstanding of the difference between the terms “serious” and “severe,” which are not synonymous, the following note of clarification is provided:

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. After reviewing the various regulatory and other definitions in use or under discussion elsewhere, the following definition is believed to encompass the spirit and meaning of them all:

A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose:

• results in death,

• is life-threatening,

NOTE: The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at 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.

• requires inpatient hospitalisation or prolongation of existing hospitalisation,

• results in persistent or significant disability/incapacity, or

• is a congenital anomaly/birth defect.

Medical and scientific judgement should be exercised in deciding whether expedited reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardise the patient or may require intervention to prevent one of the other outcomes listed in the definition above. These should also usually be considered serious.

Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalisation; or development of drug dependency or drug abuse.