16. Participant Safety

16.1 Monitoring

There are two types of monitoring of clinical trials:

  1. To assess compliance

    As per ICH E6 Guideline for Good Clinical Practice (GCP) for trials that involve human participants, trails should be monitored to protect participants, verify data integrity, and ensure compliance with GCP and regulatory requirements. The sponsor of the trial appoints a monitor who conducts monitoring in accordance with the site SOPs and the trial specific monitoring plan developed from the protocol in consideration of the risk to participants.

    For Health Canada approved Investigator Initiated Clinical Trials, the sponsor may be either the Principal Investigator or the University, and as such take on all the responsibilities of an industry sponsor. For more information on ICH Guidelines for monitoring see section 5.18

  2. Data and safety monitoring

    A Data and Safety Monitoring Board (DSMB) is an independent group of experts who monitor the trial for participant safety, data quality and study performance. The DSMB makes recommendations concerning the continuation, modification, or termination of the trial. The number of DSMB members and meeting frequency are determined by the size and complexity of the trial, but a meeting may be called at any time if there is a concern regarding patient safety. The National Institute of Aging of the National Institutes of Health has developed a set of tools for data and safety monitoring, including:

16.2 Research Reporting

16.2.1 Adverse Events

Adverse event and unanticipated problems reporting is required for all research studies regardless of whether it is a clinical or non-clinical trial, or sponsor or investigator initiated. Adverse event collection should document unfavourable changes in 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 investigator must ensure the protocol outlines how adverse events will be defined, documented and monitored at the site and subsequently reported to the sponsor(s), Health Canada, applicable regulatory authorities (e.g. FDA, US Department of Health and Human Services) and the Research Ethics Board (REB).

Information about U of Manitoba adverse event reporting can be found here and the Adverse Events Report Form can be found here

Adverse events guidelines and templates developed by the National Institute of Aging of the National Institutes of Health:

16.2.2 Protocol Deviations/Violations

Protocol deviations are activities that diverge from the Institutional Review Board approved protocol, whether deliberate or unintended. Deviations are classified as either "minor" or "major" and can be classified as a "deviation" or "violation".

Examples of minor protocol deviations, such as a minor deviation in testing time or a wording adjustment on a questionnaire may not require immediate reporting to the institutional ethics board (e.g. these are typically reported annually or on the final study status report) whereas the reporting of major protocol violations should occur in a timely manner.

According to the NIH, major protocol deviations (also called violations) occur when the divergence, whether deliberate or not, materially "(a) reduces the quality or completeness of the data, (b) makes the Informed Consent Form inaccurate, or (c) impacts a subject's safety, rights, or welfare."

Examples of major protocol deviations or violations include the following:

  • Inadequate or poor informed consent or consenting procedures
  • Enrolling a participant that does not meet eligibility (i.e. Inclusion/exclusion criteria not met)
  • Unreported serious adverse events
  • Improper breaking of the blind
  • Use of prohibited or restricted medication or misuse of the study medication
  • Incorrect or missing assessments or tests
  • Mishandled biological samples
  • Multiple visits missed or outside permissible windows
  • Intentional deviation from protocol, Good Clinical Practice, or regulations by study personnel
  • Subject repeated non-compliance with study requirements

(Source: Goldfarb, N, Journal of Clinical Research Best Practices Nov. 2005)

According to section 4.5.2 of ICH-GCP (E6 R2), "no deviations from, or change of, the protocol should be initiated without the prior written IRB/IEC approval/favorable opinion of an appropriate amendment, except when necessary to eliminate immediate hazards to the subjects or when the change(s) involves only logistical or administrative aspects of the trial" (e.g. changes in telephone #'s). Section 6.15 of the Tri-Council Policy Statement 2 (TCPS2), states that Researchers are obligated to report to their institutional ethics review board (REB)"any unanticipated issue or event that may increase the level of risk to participants, or has ethical implications that may affect the participant's welfare."

For more information on the required reporting of protocol deviations, visit University of Manitoba Ethics Medicine

16.2.3 Privacy Breaches

Any persons associated with the WRHA or WRHA Health Care Facility who have received a complaint or who have knowledge of a privacy breach of personal health information or reasonable suspicion of a privacy breach, shall immediately notify their manager or Privacy Officer at their site or the WRHA Chief Privacy Officer. More information can be found in the WRHA Privacy Policy.

Privacy breaches should also be reported to the University of Manitoba Research Ethics Board as a protocol deviation on the Major Protocol Deviation Form.

16.2.4 Participant Complaints or Questions

Provide the phone number of the University of Manitoba Bannatyne Campus Research Ethics Board (204 789-3389) to any participant that has complaints about the research or questions about his or her rights when participating in research.