Sites Safety Reporting: FAQs
Quorum Review IRB requires sites to submit reports of Serious Adverse Events (SAEs) that meet the criteria below:
- Unanticipated; and
- Related to the study product or study procedures.
If an adverse event meets all three requirements, it is a reportable SAE. An “unanticipated” adverse event is one that is not identified in nature, severity, or frequency in the relevant safety documents(s) for the study product or is not identified as a possible risk in the study protocol or the informed consent form for the study. Investigators must report an SAE to Quorum Review IRB within ten (10) business days of becoming aware of the event’s occurrence. Please use Quorum Review IRB’s Serious Adverse Event Report form. An adverse event that does not meet all three reporting criteria listed above does not need to be reported to Quorum.
Safety information and other reportable events can be submitted to Quorum Review IRB using the OnQ portal, fax or mail. All safety information should be submitted using the appropriate report forms found on the Quorum website. Quorum expects investigators to report safety information and other reportable events to Quorum Review IRB within ten (10) business days of becoming aware of the event’s occurrence.
What is a potential “unanticipated problem involving risk to participants or others” (“Unanticipated Problem”)?
Federal regulations require IRBs to collect reports of potential “unanticipated problems involving risk to participants or others” (“Unanticipated Problems”). Unanticipated Problems are events that occur during the course of a research trial that potentially increase the risk to participants or others; adversely affect the rights, safety, or welfare of participants; or affect the integrity of the study. An “unanticipated” event is one that is not identified in nature, severity, or frequency in the relevant safety documents(s) for the study product or is not identified as a possible risk in the study protocol or the informed consent form for the study.
A reportable event can occur in either a clinical setting (such as a serious and unanticipated reaction to the study drug) or a non-clinical setting (such as the loss of a laptop with study data). The event is reportable if it poses risk to research participants, research staff, or others and is possibly related to the study.
It is ultimately the decision of the Board whether a reportable event constitutes an Unanticipated Problem. In the U.S., Quorum is required to report a Board determination of an Unanticipated Problem to the FDA, OHRP or other appropriate oversight agency.
Quorum considers the following events to be potential Unanticipated Problems and requires investigators to promptly report each of the following events within ten (10) business days of becoming aware of the event’s occurrence:
- Serious adverse events
- Major protocol deviations/violations
- Research participant complaints
- Adverse audit or enforcement actions (e.g., Form FDA 483, FDA Warning Letters, FDA Establishment Inspection Reports (EIRs), adverse Sponsor audit findings, etc.)
- IND Safety Reports that qualify as unanticipated problems involving risk to participants or others
- New/updated safety information that may increase risk to participants
- Reports, publications, or interim results or findings
- Recalls, wthdrawals, or clinical holds
- Any other incident that could qualify as an unanticipated problem involving risk to participants or others, such as the loss of a laptop with confidential study data (more examples below)
- Any incident that must be reported according to the policies of the sponsor or site
For additional guidelines regarding the types of incidents that require prompt reporting, refer to the Safety Information and Unanticipated Problems Reporting Guidelines.
Do I need to submit protocol-level safety information such as IND Safety Letters and revised Investigators’ Brochures?
Investigators are expected to submit all safety information to Quorum unless the sponsor/CRO study contact for a multi-site study has arranged with Quorum to assume responsibility for submitting such information on behalf of the investigators. Please contact the sponsor/CRO or Quorum’s Site Support Team if you are not sure whether the sponsor/CRO for your study has made these arrangements.
Under Quorum’s guidelines, the vast majority of IND Safety Reports, MedWatch Reports and CIOMS Reports (“Reports”) do not need to be reported to Quorum Review. The only Reports that must be submitted are those that qualify as potential unanticipated problems involving risk to participants or others.
We understand that a number of sponsors and sites have SOPs that require transmission of all Reports to the Board regardless of the nature of the incident reported. If you are submitting a Report to fulfill such a requirement, you can so indicate on the cover page. You will receive an acknowledgment of receipt by Quorum.
Quorum Review IRB requires sites to report only major protocol deviations. A “major” protocol deviation is a protocol deviation that adversely affects the:
- Safety or welfare of research participants or others;
- Rights of research participants or others; or
- Integrity of the study design
Investigators must report a major protocol deviation to Quorum Review IRB within ten (10) business days of becoming aware of the event’s occurrence. Please use Quorum Review IRB’s Major Protocol Deviation Report form.
Under Quorum’s guidelines, examples of major protocol deviations include:
- Failure to obtain informed consent
- Informed consent obtained after the initiation of study procedures
- Omitting study procedure(s) required by approved protocol
- Performing a study procedure that is not outlined in the IRB-approved protocol
- Failure to report a Serious Adverse Event
- Drug dispensing/dosing error
- Failure to securely control the study product
- Enrolling participants outside of inclusion criteria
- Failure to follow a Safety Monitoring plan
- Study visit outside of window, only if in the opinion of the investigator, if affects the safety or welfare of the research participants or others, the rights or participants or other or the integrity of the study design.
- Use of an unapproved consent form
A minor protocol deviation is a protocol violation that, in the investigator’s judgment, does not adversely affect the risk/benefit ratio of the study, the rights, safety, or welfare of the participants or others, or the integrity of the study. Examples of minor protocol deviations include:
- Study procedure conducted out of timeframe
- Study visit out of timeframe
- Participant failure to initial every page of the consent form
- Copy of consent form not given to participant during informed consent process
- Site over-enrollment
- Participant failure to return diary
- Missing original signed consent, but have a copy of the participant signed consent
Minor protocol violations do not need to be reported to Quorum Review IRB.
Quorum considers major protocol deviations and SAEs to be potential Unanticipated Problems. Additional examples of potential Unanticipated Problems that should be promptly reported include:
- Unresolved research participant complaints
- Adverse audit or enforcement actions
- Breaches of privacy/confidentiality
- Unauthorized use or disclosure of protected health information (PHI)
- Loss of study records
- Disappearance of study drug
- Research staff misconduct affecting the research
- Incarceration of a research participant
- Injury sustained by research staff relating to the study
- Suspension of principal investigator’s medical license
- Higher than expected volume of adverse events
- Higher than expected volume of protocol deviations
- Higher than expected volume of participant drop-out rates
- Complaint from a research participant involving an unanticipated risk that cannot be resolved by the research staff
- New findings that may influence a research participant’s willingness to continue participation in the study
Do sites need to submit reports of adverse events, minor protocol deviations or other minor problems to Quorum Review?
As a general rule, no. Examples of events that generally do not need to be reported to Quorum include:
- Adverse events that, in the PI’s judgment, are not related to the study (such as a participant catching the flu);
- Adverse events that are anticipated or expected as part of the study (such as nausea in a trial of a chemotherapy drug);
- IND Safety Reports that, in the PI’s judgment, do not adversely affect the conduct of the PI’s study at his/her research facility;
- Minor protocol deviations (such as study visits performed slightly out of window);
- Minor research participant complaints that are adequately resolved by the research staff.
At the time of periodic site review, Quorum Review IRB’s “Sites Status Report for Periodic Site Review” will ask whether the investigator believes that a change in the research plan or the consent form is necessary in light of these unreported events. If the investigator recommends a change in the research or the consent form, Quorum Review IRB might request that the investigator submit the log or other summary of adverse events and protocol deviations for further consideration.
What should I do if the sponsor’s guidelines require me to submit a report but under Quorum’s guidelines the event is not reportable?
Quorum Review IRB recognizes that sponsors, site monitors, CROs or sites may have broader reporting requirements than Quorum’s. You can go ahead and submit such reports. Quorum Review IRB will provide a standard acknowledgement of all documents submitted to fulfill such sponsor and site requirements.
If you are submitting multiple IND Safety Reports (or other events) at the same time, we encourage you to include a cover letter listing all of the reports included in the submission.
For centralized multi-site studies, Quorum Review IRB requests that sponsors submit the following documents on behalf of the investigators:
- Investigator Brochures
- Package Inserts
- Device Manuals
A protocol “waiver” or “exception” is an intentional deviation from the approved protocol, such as the enrollment of a participant in violation of the protocol’s inclusion/exclusion criteria. Most sites realize that it is necessary to obtain the sponsor’s approval prior to implementing a protocol waiver. It is also necessary, however, to obtain the IRB’s approval prior to implementing a protocol waiver, unless the change is deemed necessary to eliminate an apparent immediate hazard.
All requests for protocol waivers should be submitted to Quorum on Quorum’s Prospective Waiver Request Form. Quorum will ask for documentation of the sponsor’s approval and each request will be submitted to the Board. Such requests typically are processed through Quorum’s expedited Board reviewers.
Please submit a protocol deviation report to notify Quorum of changes made from the approved protocol without prior approval. The change is reportable if it meets the reporting criteria for major protocol deviations.
A standard acknowledgment is an acknowledgement of receipt. Quorum Review IRB will stamp the first page of a submitted safety report with the Quorum Review IRB “Received” stamp and return a copy of the stamped first page to the investigator.
Please note that standard acknowledgment represents receipt only; the standard acknowledgement does not represent Board review of the reported information. The Board will send a separate notice if it is determined upon review that additional action is necessary. In a multi-site study in which a number of investigators submit duplicate information (such as IND Safety Reports), Quorum will return a standard acknowledgment to each investigator who sends a submission.