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Safety Reporting and Monitoring Adverse Events

Procedures for reporting of adverse events and safety information to CHIPER are based on the Canadian Association of Research Ethics Boards Guidance on Reporting of Unanticipated Problems, including Adverse Events to Research Ethics Boards in Canada (July 2010).

Definitions 

Adverse event (AE): Any untoward or unfavorable medical occurrence in a human participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the individual’s participation in the research, whether or not considered related to the individual’s participation in the research. Adverse events encompass both physical and psychological harms. They occur most commonly in the context of biomedical research, although on occasion, they can occur in the context of social and behavioral research.

External (non-local) Adverse Event (EAE): Adverse events experienced by research participants enrolled by researchers at centers/institutions outside RITHIM’s jurisdiction.

Local (internal) Adverse Event: Adverse events experienced by research participants enrolled by the researcher at one or more centers/sites under the jurisdiction of RITHIM. In the context of a single-center clinical trial, all adverse events would be considered local adverse events.

Serious Adverse Event (SAE): is an adverse event that

  • Results in death; or
  • Is life-threatening; or
  • Requires in-patient hospitalization or prolongation of existing hospitalization; or
  • Results in persistent or significant disability or incapacity; or
  • Causes congenital malformation/birth defect; or
  • Any other adverse event that, based on appropriate medical judgment, is an important medical event that may jeopardize the health (physical, psychological, economic or social) of the research participant or may require medical intervention to prevent one of the outcomes listed above.

Unanticipated Problem: any incident, experience, or outcome that meets all of the following criteria:

  • Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the approved research protocol, informed consent document(s), or Investigator’s Brochure; and (b) the characteristics of the research participant population being studied; and
  • Related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the investigational product(s) or procedures involved in the research); and
  • Suggests that the research places research participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Adverse Event Collection and Reporting of Unanticipated Problems 

Adverse event or unanticipated problems collection and reporting are required for all research projects whether a project is clinical or non-clinical in nature, or sponsor- or investigator-initiated.

Adverse event collection should document unfavorable changes in the current health status of the research participant or any incident, experience or outcome that suggests that the research may place participants or others at a greater risk of harm (including physical, psychological, economic, or social harm).

The researcher must ensure the protocol outlines how adverse events will be defined, documented and monitored at the site and subsequently reported to the sponsor(s), CHIPER, and applicable regulatory authorities — such as Health Canada or the FDA, US Department of Health and Human Services. The researcher should review the applicable regulatory authority website for guidance on reporting requirements to regulatory agencies.

Local Adverse Events 

Criteria and submitting instructions

  • Report only those local adverse events that are considered unanticipated problems (i.e., unexpected, related or possibly related and places participants at greater risk).
  • The reporting requirements apply to non-intervention trials as well as intervention (clinical) trials.
  • Submit all fatal or life-threatening adverse events that are unexpected and related or possibly related (i.e., unanticipated problems) to CHIPER within seven days of becoming aware of the event.
  • Submit all other unanticipated problems (local) and reportable adverse events to CHIPER within 15 days of becoming aware of the event.
  • Serious adverse events must also be reported to the project sponsor, as the sponsor is responsible for submitting safety information to applicable regulatory authorities.
  • When the project is funded by the US Department of Health and Human Services (e.g., NIH, CDC, or other) the sponsor or lead Principal Investigator is also responsible to report the unanticipated local adverse event and other local unanticipated problems to the applicable agency head (or designee) and the Office of Human Research Protections within one month of becoming aware of the event on behalf of applicable institution.
  • Changes required to the protocol or informed consent form as a result of the unanticipated problem/ adverse event(s) must be submitted through an Amendment to the Health Research Application in Harmony.

Non-local Adverse Events 

Only external adverse events (EAE) that meet the following criteria are to be reported in Harmony:

  • Meet the definition of Unanticipated Problem (see definition above); and
  • Require a change to the protocol and/or informed consent form, and/or require immediate notification to participants for safety reasons.

Only reports that include ALL of the following will be accepted:

  • The description of the serious and unexpected event and why it is considered an unanticipated problem; and
  • All the previous safety reports concerning similar adverse events; and
  • An analysis of the significance of the current adverse event in light of the previous reports; and
  • The proposed protocol changes, informed consent form changes or other corrective actions to be taken by the sponsor in response to the event.

Submitting Instructions 

Prior to submitting an EAE in Harmony, it is the researcher’s responsibility to review the report to ensure it meets the reporting criteria outlined above.

Complete and submit the Harmony Reportable Events Form for each event along with a copy of the sponsor generated report within 15 days of becoming aware of the unanticipated EAEs.

Incomplete submissions or submissions that do not meet the criteria listed above will not be accepted.

Sponsor documents must meet the reporting criteria listed above or the EAE report will not be accepted.

Changes required to the project protocol or informed consent form(s) as a result of EAE(s) must be submitted through an Amendment to the Health Research Application in Harmony.

Periodic Safety Updates 

Periodic safety update reports are sponsor-generated compilations of suspected unexpected serious adverse reactions (SUSARs) and/or other external adverse events that occurred during a particular reporting period (typically quarterly, semi-annual, or annual), with a summary highlighting any main points of concern and the evolving safety profile of the investigational product.

Periodic safety update reports will be accepted in Harmony, provided the report highlights the main points of concerns and the evolving safety profile of the investigational product.

Submitting instructions 

Upon receipt of the Periodic Safety Report from the sponsor, it is the investigator’s responsibility to review each report to ensure it meets the reporting criteria outlined above.

Complete and submit the Reportable Events Form in Harmony for each report along with a copy of the sponsor-generated report within 30 days of receipt.

Incomplete submissions, or submissions that do not meet the criteria listed above, will not be accepted.

Sponsor documents must meet the reporting criteria listed above or the report will not be accepted.

Changes required to the project protocol or informed consent form(s) as a result of the adverse events outlined in the Periodic Safety Report must be submitted through an Amendment to the Health Research Application in Harmony.

Updated Safety Information 

In accordance with Articles 11.8 and 11.9 of the TCPS 2, researchers are required to promptly report new information that may affect the welfare and consent of participants in Harmony.

Examples of updated project safety information include, but are not limited to the following:

  • Data Safety Monitoring Board (DSMB) report,
  • Audit or monitoring report,
  • Interim project results,
  • Health Canada, FDA or other regulatory agency project results,
  • Safety alerts,
  • Publication in the literature or other findings,
  • Any suspension, restriction or revoking of the researchers’ medical/dental license or hospital privileges,
  • Notification of suspension or termination of the project,
  • Changes in the Health Canada or FDA labeling or withdrawal from marketing of a drug, biologic or device used in a research protocol.,

Submitting instructions 

In each instance, complete and submit the Reportable Events Form in Harmony, along with an electronic copy of the sponsor generated report.

Updated safety information which suggests increased risk and immediate safety concerns to participants or any suspension or premature termination of the project should be reported immediately upon becoming aware of the information. All other updated safety information should be reported within 30 days of becoming aware of the report (e.g., DSMB report that suggests trial may continue as planned, new Investigators Brochure that does not require immediate notification of risks to participants, etc.).

Any changes as result of the safety update information required to the protocol or informed consent form must be submitted through an Amendment to the Health Research Application in Harmony.