Human Research Protections Office (HRPO)

I.3.J:           Reportable Events (Unanticipated Problems, Adverse

                   Events, Deviations, Violations, Exceptions)

Policy:  The UMB HRPP and IRB’s policy is to comply with all applicable local, state, and federal regulations in the conduct of research studies. Written procedures are required for processing reports of events that may represent unanticipated problems involving risks to participants and others.  Principal Investigators (PIs) are required to report the following for review:

§  Unanticipated Problems Involving Risks to Research Participants or Others (UPs) as soon as they become aware, but in all cases within two (2) working days for internal events and five (5) working days for external events.

§  Violations must be reported to the IRB within two (2) working days of occurrence or of the PI or study personnel becoming aware of the violation. 

§  Protocol Deviations (PD) that do not alter the risk benefit analysis or integrity of the study can be submitted at the time of annual renewal or in an expedited fashion if the sponsor requires such reporting. 

§  Protocol Exception (PE) requests must be submitted and receive IRB approval prior to implementing the proposed deviation.

 

Definitions:

·                    Deviation:  Any difference in study conduct from the criteria or procedures prescribed in the approved protocol, which may or may not affect the participants’ rights, safety, welfare, and/or the integrity of the study and resultant data.  Deviations may result from the action of the participant, investigator, or staff.

·                    Protocol Exception:  A deviation approved by the IRB prior to implementation.

·                    Violation: A deviation that affects the participant’s rights, safety, welfare, and/or the integrity of the resultant data.     

·                    Unanticipated Problems Involving Risks to Research Participants or Others (UP): An event (including on-site and off-site adverse event reports, injuries, side effects, breaches of confidentiality, deaths, or other problems) that occurs any time during or after the research study, which in the opinion of the PI:

1.                   Involves harm to one or more participants or others, or placed one or more participants or others at increased risk of harm AND

2.                   is Unexpected  AND

3.                   is Related to the research procedures

 

These include but are not limited to:

A.                  Information that indicates a change to the risks or potential benefits of the research, in terms of severity or frequency. For example:

1.                    An interim analysis indicates that participants receiving investigational vaccine have a higher rate of contracting the disease than participants receiving placebo

2.                    Safety monitoring indicates that a particular side effect is more severe, or more frequent than initially expected

3.                    A paper is published from another study that shows that an arm of your research study is of no therapeutic value

B.                   Change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol.

C.                  Event that requires prompt reporting to the sponsor

D.                  Sponsor imposed suspension for risk

E.                   Complaint of a participant when the complaint indicates unexpected risks or cannot be resolved by the research team

F.                   Unanticipated adverse device effect (Any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.)

G.                  Change to the protocol taken without prior IRB review to an eliminate apparent immediate hazard to a research participant

H.                  Incarceration of a participant

I.                    Protocol violation (meaning an accidental or unintentional change to the IRB approved protocol) that placed one or more participants at increased risk, or has the potential to occur again

 

Process and Rationale:         

 

I.                    All questions received by the HRPO in regards to a Reportable Events should be referred to a Research Subject Advocate and Safety Specialist

 

II.                  The Research Subject Advocate and Safety Specialist (RSASS) will review all reportable events for appropriateness, completeness, and determination as to whether the event is an unanticipated problem involving risk to participants or others. The RSASS may send events to an IRB Chair/Vice-Chair for determination if needed.

 

Unanticipated Problems Involving Risk to Research

Participants or Others (UPs)

 

Policy: It is the policy of theUniversity of Maryland, Baltimore (UMB) Institutional Review Board (IRB) to review reports of unanticipated problems involving risk to participants or others in research activities under its jurisdiction. The IRB Chair has appointed the Research Subject Advocate and Safety Specialist (RSASS) to review reportable events and acknowledge adverse event reports.

 

Process and Rationale:

 

III.                PIs are required to report:

A.                  Unanticipated Problems Involving Risk to Research Participants or Others

 

B.                   Adverse events that are unexpected and related to the research even if they are not serious adverse events.

C.                  External adverse events which are unanticipated problems involving risk to participants or others

D.                  Changes made to the research without prior IRB approval in order to eliminate apparent immediate hazard to the participants

E.                   Adverse events and UPs using the AE Form in BRAAN

F.                   Violations using the Protocol Deviation Form in BRAAN.

 

IV.                An UP can be reported using the AE Form in BRAAN at any time, regardless of whether or not there is another transaction currently in progress or if the study is closed.  When applicable, the PI is to submit an amendment in BRAAN indicating changes associated with the UP. 

 

V.                  The PI should:

A.                  Provide a summary of the UP in the text box labeled “adverse event information.”  (This box may be used for all reportable problems).  The summary should include type or nature of the problem, a full description of the activities leading to the problem, interventions/actions taken in response, temporal relationship of event to the use of the investigational product/procedure and the current status of the participant.

B.                   If the consent form will not be modified, the Investigator should justify why the consent form will not be revised.

C.                  If necessary, attach additional documentation as described under the blue box labeled “attachment.”

D.                  Answer the templated questions that indicate the date of the event, the participant’s study number, the site, the classification of the event, the relationship to the study, if the consent will be modified, if the event is expected as natural progression of disease, and if the unanticipated problem involving risks to participants or others is a result of an exception or deviation. 

E.                   Select “UMB Site” when the event occurred to a participant consented with a UMB consent document and under the UMB IRB purview.  If the event affected an individual “other” than a participant, select “UMB Site” when the event occurred in relation to any aspect of the study under UMB IRB purview. 

 

VI.                The PI is responsible for the accurate documentation, investigation, and follow-up of unanticipated problems involving risk to participants or others.

 

VII.              The PI is responsible for informing the sponsor or funding agency of any UP in accordance with Institutional policies and procedures.

 

Research Subject Advocate and Safety Specialist:  UPs

 

VIII.            If the report requires immediate action before receipt of a completed report, the Research Subject Advocate and Safety Specialist will send the information immediately to the IRB Chair or Vice Chair on duty for the day.

 

IX.                If the PI indicates the event was: (1) foreseen, (2) did not cause harm or did not place a person at increased risk of harm, OR (3) was not related to the research procedures and the Research Subject Advocate and Safety Specialist considers the submitted information to be consistent with the investigator’s assessment, the event is not considered to be an UP, and may request the Investigator to “withdraw” the AE Report from IRB review through the BRAAN system.

A.                  If the PI indicated that the consent document, or protocol should be revised, or that currently enrolled participants should be notified, then the Research Subject Advocate and Safety Specialist requests that the Investigator submit an Amendment to the IRB for review of proposed modifications to previously approved research.

 

X.                  If after consultation with the IRB chair or Vice Chair, the Research Subject Advocate and Safety Specialist considers the submitted information to be:

A.                  inconsistent with the investigator’s assessment or have reason to doubt the determinations of the investigator, OR

B.                   the Investigator indicates the event (1) was unforeseen, (2) caused harm or placed a person at increased risk of harm, AND (3) was related to the research procedures, the Research Subject Advocate and Safety Specialist will notify the HPA, the Director of Compliance and Quality Improvement, and the Director of IRB Operations and the event will be placed on the agenda of the next available IRB meeting for review. 

 

XI.                University Counsel or Risk Management should be consulted as needed.

 

Protocol Deviations and Violations

 

XII.              It is the responsibility of the PI not to deviate from the protocol approved by the IRB, except to avoid an immediate hazard to the participant.  The PI must submit an amendment request to the IRB and receive written approval prior to implementation of any change to the protocol.

 

XIII.            The PI will monitor research activities for adherence to the protocol and determine if protocol deviations and/or violations have occurred.

 

XIV.            PIs should report protocol violations and deviations using the protocol deviation report form in BRAAN.  Violations and deviations can be submitted at any time, regardless of whether or not there is another transaction currently in progress

 

XV.              The PI should:

A.                  Provide a description of the deviation.  The description should include a summary of events leading to the deviation, interventions or actions taken as a result of the deviation and steps that will be taken to prevent similar deviations in the future.

B.                   Answer the templated questions that indicate the date of the event, if the event resulted in an UP or adverse event, if the participant will continue in the research study and the participant’s study number.

C.                   Discuss the impact the deviation will have on the participant’s rights, safety, and/or welfare.

D.                  Discuss the impact the deviation will have on the scientific integrity of the study.

 

XVI.            The PI is responsible for the accurate documentation, investigation, and follow-up of violations and deviations.

 

Protocol Exception Requests

 

XVII.          The Investigator will submit any anticipated changes in the conduct of the protocol to the IRB for review and approval prior to implementation. 

 

XVIII.        PIs should request a protocol exception using the protocol exception request form in BRAAN.  Protocol Exceptions can be requested at any time, regardless of whether or not there is another transaction currently in progress.

 

XIX.            The PI should:

A.                  Describe the exception being requested and provide the rationale for the request. 

B.                   Discuss how the requested departure from the protocol could affect the participant’s safety.

C.                  Discuss the impact the exception would have on the scientific integrity of the study.

D.                  Indicate if the sponsor is aware and has approved of the proposed exception.

 

XX.              A sponsor’s approval of a proposed exception request does not guarantee IRB approval of the request.   Anticipated departures from approved protocol practice must receive IRB approval prior to implementation.

 

XXI.            In general, protocol exceptions apply to one participant/issue/occurrence.  Protocol exceptions are not to be used in lieu of a protocol amendment. 

 

Protocol Deviations (PD) and Exceptions (PE)

 

XXII.          If the PD or PE report requires immediate action, the Research Subject Advocate and Safety Specialist will send the information immediately to the IRB Chair or Vice Chair on duty for the day.

 

XXIII.        If the deviation represents an UP the IRB Chair or Vice Chair on duty for the day, as well as the HPA, the Director of Compliance and Director of IRB Operations, will be notified.  The report will be placed on the agenda of the next available IRB meeting.

 

XXIV.        Additionally, a protocol deviation report can be assigned to full board at the request of the IRB Chair or Vice Chair. 

 

Review by the Fully Convened IRB

 

XXV.          The IRB reviews events that represent UPs regardless of level of risk to participants as follows:

A.                  The Primary Reviewer and all IRB members have access to the UP, AE or PD Report and are provided supporting documents from the Principal Investigator as applicable.  The electronic protocol management system also provides access to the following protocol-related documents:

1.                   The currently approved protocol

2.                   The currently approved consent document

3.                   Previous reports of unanticipated problems involving risks to participants or others for the protocol

4.                   The investigator’s brochure, if one exists

B.                   The IRB considers the following actions:

1.                   Suspension of the research

2.                   Termination of the research

3.                   Notification of current participants when such information may relate to participants’ willingness to continue to take part in the research.

4.                   Modification of the protocol

5.                   Modification of the information disclosed during the consent process

6.                   Providing additional information to past participants

7.                   Requiring current participants to re-consent to participation

8.                   Modification of the continuing review schedule

9.                   Monitoring the research

10.               Monitoring the consent process

11.               Requiring additional training of the investigator

12.               Notification of investigators at other sites

13.               Obtaining additional information

C.                  Reporting requirements will be followed as applicable (SOP I.3.N).