Sponsors and CROs safety reporting
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General Guidance
Quorum Review IRB requires reporting of all events that may constitute unanticipated problems involving risk to research participants or others as well as new or updated safety information relating to the study or study product. Reportable events/information must be reported to Quorum within 10 business days of their occurrence.Protocol Level Safety Information and Unanticipated Problems
Typically, the investigator is responsible for submitting safety information; however, Quorum Review IRB allows the sponsor to accept responsibility for submitting study-wide safety information to Quorum on behalf of all investigators involved with the study. The sponsor can make this choice by providing the appropriate information on the "Central Study Questionnaire."The following study-wide safety information should be submitted to Quorum Review IRB when such information qualifies as a Reportable Event:
- IND Safety Reports (i.e., external adverse events)
- Device Reports
- Data Safety Monitoring Board (DSMB) Summary Reports
- FDA or sponsor Safety Alerts
- Notification of product withdrawals
- Recalls and clinical holds
- Other relevant safety information
Investigator Brochures, Package Inserts, and Device Manuals
Quorum Review IRB requests that sponsors accept responsibility for submitting the following documents on behalf of investigators:- Investigator Brochures
- Package Inserts
- Device Manuals
When Investigator Brochures, Package Inserts, and Device Manuals are revised, Quorum Review IRB requires sponsors to submit a summary of changes along with the revised document to Quorum Review IRB on behalf of all investigators at the same time these revised documents are sent to investigators. In addition, it is especially helpful to provide a tracked version of the document showing the changes made.
Required
F-018 - Protocol Deviation (Major) /Violation Report
Use this form for reporting Major Protocol Deviations / Violations.
F-022 - Serious Adverse Event Report
Use this form for all Serious Adverse Events that occur at the Principal Investigator's site.
F-035 - Prospective Protocol Waiver/Exception Request Form
Use this form to request Board review of prospective Protocol Waivers / Exceptions. You must receive Board approval before initiating any change to the research.
Recommended
F-021 - Safety Information and Unanticipated Problem Cover Page
Use this form for all Safety Information and Unanticipated Problems that occur external to the PI's site and meet Quorum reporting requirements
F-024 - Unanticipated Problem Report
Use this form for all Unanticipated Problems meeting Quorum Review's reporting requirements that occur at the Principal Investigator's research site.
Guidance
G-036 - Safety Information and Unanticipated Problems Guidelines
This guidance document provides a listing of the safety events that could be reported to Quorum, examples of the events, reporting criteria, and what forms to use to report the events to Quorum.
G-042 - Safety and Unanticipated Problems Powerpoint
Powerpoint presentation on when, and how, to report safety information to Quorum Review.
G-043 - Handbook for Quorum Review IRB (Requires an OnQ Portal Account)
The Handbook provides a guide for using Quorum Review IRB as an ethics review board. It contains policies, procedures, and guidelines to be used in preparing materials for Board review, as well as information on managing ongoing research activities, continuing and periodic review, and closing.
Q. How should I submit safety information and potential unanticipated problems to Quorum Review IRB? >>
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.
Q. 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.
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.
Q. What safety information should be reported to Quorum? >>
Quorum requires investigators to promptly report each of the following events within ten (10) business days of becoming aware of the event’s occurrence:
For additional guidelines regarding the types of incidents that require prompt reporting, refer to the Safety Information and Unanticipated Problems Reporting Guidelines.
- 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, Withdrawals, 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.
Q. Do I need to submit protocol-level safety information? >>
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.
Q. When should sites report serious adverse events to Quorum? >>
Quorum Review IRB requires sites to submit reports of all Serious Adverse Events (SAEs). Only the adverse events that meet the criteria below need to be reported:
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 requirements is not an SAE and does not need to be reported to Quorum Review IRB. Quorum does not collect reports of adverse events that are not SAEs.
- Serious;
- 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 requirements is not an SAE and does not need to be reported to Quorum Review IRB. Quorum does not collect reports of adverse events that are not SAEs.
Q. When should sites report a protocol deviation to Quorum? >>
Quorum Review IRB requires sites to report only major protocol deviations. A "major" protocol deviation is a protocol deviation that adversely affects the:
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.
- 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.
Q. What is a "major" protocol deviation? >>
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
Q. What is a "minor" protocol deviation? >>
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:
Minor protocol violations do not need to be reported to Quorum Review IRB.
- 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.
Q. What is a potential "unanticipated problem involving risk to participants or others"? >>
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 Unanticipated Problem can occur in either a clinical or a non-clinical setting and is reportable if it poses risk to research participants, research staff, or others. Quorum expects investigators to report potential Unanticipated Problems to Quorum Review IRB within ten (10) business days of becoming aware of the event’s occurrence.
Q. What are some examples of potential Unanticipated Problems? >>
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
Q. 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:
"yes", then Quorum asks that the site submit an analysis of the unreported events and a rationale for suggested changes to the study plan.
- 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.
"yes", then Quorum asks that the site submit an analysis of the unreported events and a rationale for suggested changes to the study plan.
Q. What should a site do if a sponsor’s reporting guidelines require the submission of all serious adverse events and major protocol deviations even if they do not meet Quorum’s reporting criteria? >>
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.
Q. Do I need to submit all IND Safety Reports for this study to Quorum? >>
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.
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.
Q. What should I do if I have several different IND Safety Reports to submit at one time? >>
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.
Q. Who should submit changes to Investigator Brochures, Package Inserts, or Device Manuals? >>
For centralized multi-site studies, Quorum Review IRB requests that sponsors submit the following documents on behalf of the investigators:
When Investigator Brochures, Package Inserts, and Device Manuals are revised, Quorum Review IRB requires sponsors to submit a summary of changes along with the revised document to Quorum Review IRB on behalf of all investigators at the same time these revised documents are sent to investigators. In addition, it is especially helpful to provide a tracked version of the document showing the changes made.
- Investigator Brochures
- Package Inserts
- Device Manuals
When Investigator Brochures, Package Inserts, and Device Manuals are revised, Quorum Review IRB requires sponsors to submit a summary of changes along with the revised document to Quorum Review IRB on behalf of all investigators at the same time these revised documents are sent to investigators. In addition, it is especially helpful to provide a tracked version of the document showing the changes made.
Q. Does Quorum issue approval for Investigator Brochures (IB) and other product information? >>
Quorum requires submission of an IB for the initial review of every IND protocol. The IB is important to the review of a protocol, in that it provides information that is necessary to assess the overall risks and benefits of the research; however, Quorum Review does not "approve" or "disapprove" this document.
Should the IB be updated during the course of a study, acknowledgement of the revised document is provided to the sponsor and all active sites, if requested by the sponsor, in order to document that Quorum Review has been adequately notified of additional safety information provided since the initial review.
Should the IB be updated during the course of a study, acknowledgement of the revised document is provided to the sponsor and all active sites, if requested by the sponsor, in order to document that Quorum Review has been adequately notified of additional safety information provided since the initial review.
Q. What is a "protocol waiver" or "protocol exception"? >>
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.
Q. How does a site obtain prospective (prior) permission to implement a protocol waiver? >>
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 typically processed through Quorum’s expedited Board reviewers.
Q. A site neglected to obtain IRB approval prior to implementing a protocol waiver. What should the site do now? >>
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.
Q. What is a standard acknowledgment? >>
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.
What is sponsor acknowledgement? >>
A sponsor acknowledgement is provided when a sponsor chooses to assume sole responsibility for submitting to Quorum Review IRB study-level safety information and Reportable Events (such as IND Safety Reports, Investigator Brochures, Package Inserts, and Device Manuals). Even if the sponsor assumes this responsibility; however, Quorum Review IRB will generate the acknowledgement letter upon receipt of the initial report without regard to who submitted it.
Quorum Review IRB will generate only one receipt letter per report, even if Quorum Review IRB receives multiple copies of the report. In addition, Quorum Review IRB will generate a standard stamp acknowledgement for each investigator who submits a copy of the report.
Quorum Review IRB will generate only one receipt letter per report, even if Quorum Review IRB receives multiple copies of the report. In addition, Quorum Review IRB will generate a standard stamp acknowledgement for each investigator who submits a copy of the report.
Q. What are my options for safety information acknowledgment? >>
Quorum Review IRB provides sponsors with two types of acknowledgement for Safety Information and Unanticipated Problems:
When Quorum Review IRB is reviewing a study on a single-site basis, Quorum Review IRB will always send the Standard acknowledgment as described above. When Quorum Review IRB is acting as a central Ethics Review Board, the sponsor determines the type of acknowledgement investigators will receive for study-wide reports at the time of protocol submission. The sponsor makes this choice on the "Central Study Questionnaire" (CSQ).
- Option one – sponsor acknowledgment only: Quorum Review IRB sends the receipt letter to the sponsor only. The sponsor then accepts responsibility for distributing acknowledgments to the sites as necessary.
- Option two - study-wide acknowledgment: Quorum Review IRB distributes receipt letter to each site that is open at the time of receipt. For this service, Quorum Review IRB will charge on a per site basis.
When Quorum Review IRB is reviewing a study on a single-site basis, Quorum Review IRB will always send the Standard acknowledgment as described above. When Quorum Review IRB is acting as a central Ethics Review Board, the sponsor determines the type of acknowledgement investigators will receive for study-wide reports at the time of protocol submission. The sponsor makes this choice on the "Central Study Questionnaire" (CSQ).
Q. How do I change my Safety Information acknowledgment preference? >>
You can change your acknowledgement preferences by submitting the Central Study Information Change Request Form at any time throughout the course of the study. For more information about acknowledgment options or changing acknowledgment preference contact your Study Manager.
Q. I don’t see formal acknowledgment letters for PD’s and SAE’s in the site documents. Are the site files missing something? >>
Quorum Review IRB does not send formal acknowledgement letters for site level safety Information. Quorum sends standard acknowledgements for site level safety information or Unanticipated Problems. Quorum Review IRB will stamp the first page of the document with the Quorum Review IRB "Received" stamp and return a copy of the stamped first page to the investigator.
Q. How is safety information acknowledged for a Principal Investigator Generated study? >>
Quorum will issue an acknowledgement letter to the site when a revised Investigator Brochure is received. When all other safety information is received, such as Protocol Deviations, IND safety reports, Serious Adverse Event reports, and reports of Unanticipated Problems, Quorum will issue a standard acknowledgment. In the case of a standard acknowledgement, Quorum will stamp the first page of the document with the Quorum Review IRB "Received" stamp and return a copy of the stamped first page to the investigator.