IRB Version Date: 12/2013
Saint Louis University
Institutional Review Board (IRB)
REQUIREMENTS FOR REPORTING EVENTS RELATING TO SUBJECTS/SUBJECT SAFETY
A. INTRODUCTION
In accordance with the Department of Health and Human Services (DHHS) and the Food and Drug Administration (FDA) regulations, the IRB is required to review IRB-approved research protocols on a continuing basis. It is important for researchers to be aware of IRB reporting requirements after receiving IRB approval. This document is intended to provide investigators with instructions for reporting events to the IRB during the conduct of a Saint Louis University (SLU) research protocol. It is the responsibility of the principal investigator (PI) to ensure that events are reported according to these requirements.
This document outlines only those events related to subjects or subject safety or wellbeing while participating in a research study. This is not an exhaustive list of all reporting requirements.
B. DEFINITIONS and REPORTING REQUIREMENTS
The following events require submission to the Saint Louis University IRB. Please note that these are SLU IRB definitions and requirements for submission.
Each of the next events must meet the following criteria and fit one or more of the categories (1-3) below.
§ Protocol Specific – Event occurred in a research study that is being conducted at SLU, by SLU researchers, or is otherwise under the jurisdiction of the SLU IRB, and
§ Reasonably Related – It is at least possible that the incident, experience, or outcome was caused by the procedures involved in the research (i.e., the causality is determined to be possible, probable, or definite).
1. Serious Adverse Event (SAE)- an adverse event meeting one of the following conditions:
o Results in death during the period of protocol defined surveillance (usually includes events that occur within 30 days of study completion).
o Is life threatening (defined as a subject at immediate risk of death at the time of the event).
o Requires inpatient hospitalization or prolongation of existing hospitalization during the period of protocol defined surveillance.
o Results in a congenital anomaly or birth defect.
o Results in a persistent or significant disability/incapacity.
o Any other important medical event that may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above. (Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.)
Investigators can use the SLU IRB SAE Decision Tree to assist in determining whether an event is a reportable SAE.
Reporting SAEs:
o SAEs are to be reported on the SAE Report Form (use paper form if the protocol is not in eIRB; otherwise, submit using SAE Report Form in eIRB).
o SAEs that result in death or that are life threatening must be reported to the IRB within 3 calendar days of the event or the date when the SLU study site was notified of the event. (An email notification should only be used if the report cannot be submitted within 3 calendar days.)
o Other SAEs should be reported to the IRB within 7 calendar days of the event or the date when the SLU study site was notified of the event. (An email notification should not be used.)
o If the event cannot be reported to the IRB office in the time frame mentioned above, an email notification to will suffice until an SAE form is submitted. The SAE form should be submitted as soon as possible after the email notification.
o If the SAE warrants a change to the protocol, consent form, or other research materials, the Change-in-Protocol form (Amendment in eIRB) should specify the request for changes being made to the protocol.
2. Unanticipated Problem (UP) -
o An unexpected and serious adverse event or an unexpected and serious incident, experience or outcome that is protocol specific, reasonably related, and
a. For device research, relates to the rights, safety, or welfare of the subjects,
OR, for any research:
b. The event is not consistent with or exceeds the nature, severity or frequency described in the protocol, consent form, or investigator’s brochure or is unexpected given the characteristics of the subject population being studied,
AND
c. The event suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
Investigators can use the SLU IRB UP Decision Tree to assist in determining whether an event is a reportable UP.
Note: The SLU site may receive notification of a UP from the study sponsor. Please see reporting requirements of such a notification, below.
Reporting UPs:
o UPs should be submitted on the Report Form in eIRB (Change in Protocol Form for paper protocols) unless it is also an SAE. UPs that are also SAEs should be reported on the SAE Report form.
o If the UP warrants a change, the change to study materials can be specified on an Amendment form in eIRB (Change in Protocol Form for paper protocols).
o Events that result in death or that are life threatening must be reported to the IRB within 3 calendar days of the event or the date when the SLU study site was notified of the event.
o Other UPs shall be reported to the IRB within 7 calendar days of the event or the date when the SLU study site was notified of the event. Submit sponsor UP notifications within 7 days on a Report Form. If there are changes to the protocol, submit as an amendment and note that changes are the result of a UP. See note, below.
NOTE: Most amendments that include changes to the risks, inclusion / exclusion criteria and study design are a result of an unanticipated event that occurred during the study or another similar study. As such, if an amendment is received from the sponsor, it should be submitted to the IRB as soon as possible but no later than 15 business days after receipt. The information should be evaluated as to how quickly a subject should be notified (i.e., significant changes to the risks may need to be relayed to subjects verbally until the re-consent process takes place, as the new information may affect a subject’s willingness to continue participation.) Sponsors may require approval of modified consent forms prior to submission to the IRB. If submission is being held up by sponsor review, please e-mail to notify the IRB of the expected delay in submission and provide a justification for the delay when the amendment is submitted. The e-mail notification will satisfy the IRB’s reporting requirement in these cases.
3. Protocol Violation (PV)- An unintentional variation from the approved research protocol, error in conduct of the study, or failure to get IRB approval prior to implementing a protocol deviation. PVs often occur without control of the research team (participant non-compliance) or are done in error.
Examples:
o Participant does not go to scheduled study visit, putting him/her outside of a treatment window
o Research team member accidentally gives wrong dose to participant
o Use of an invalid consent document
o Labs are drawn at the wrong visit
o Someone other than the subject dated the consent form
o Research team enrolls a participant who doesn’t meet inclusion criteria without first getting IRB approval
There are occasions when a protocol violation may be considered a failure to protect the rights, safety and welfare of participants. Notify the IRB of PVs that place a participant or others at a greater risk of harm (including physical, psychological, economic, or social harm) than if the protocol was followed as intended.
NOTE: All consent violations, and protocol deviations implemented without prior IRB approval, are considered to be reportable.
Investigators can use the SLU IRB PV Decision Tree to assist in determining whether an event is a reportable PV.
Reporting PVs:
o PVs are to be reported on the Report Form in eIRB (Change in Protocol / For Information Form for paper protocols).
o PVs that result in SAEs are to be reported on an SAE form within 3 days of the event or the date when the SLU study site was notified of the event. If the PV results in the death of a subject, also notify the IRB immediately (via phone or e-mail).
o Other PVs affecting subject safety must be reported within 7 calendar days from the date the violation becomes known.
o At the time of report, the PI should provide an explanation of what happened, why the PV occurred and a plan to prevent recurrence of such events in the future.
The following (1-6 below) do not have to meet the same criteria as those referenced above and may have nothing to do with subject safety.
1. Protocol Deviation (PD)- an intentional variation from the approved protocol. PDs are intentional (planned) and within the control of the research team. For sponsored studies, typically, sponsor approval is required before implementing. PDs must be submitted to the IRB regardless whether or not they affect subject safety.
Examples:
o Enrollment exceptions (e.g., inclusion of a participant who does not meet the inclusion/exclusion criteria)
o Participation exceptions (e.g., variation or elimination of a procedure or test for a participant)
o A subject stating at the time of enrollment they will be out of the country and will have an out of window visit but are still allowed to enroll
Reporting PDs:
o IRB approval should be obtained prior to implementing the deviation, as the IRB considers deviations to be modifications to the protocol.
o PDs should be submitted on the Amendment form in eIRB (Change in Protocol / For Information Form for paper protocols. Note: for time sensitive PDs ONLY, a call or an email to the IRB office and the IRB response will suffice until follow up paperwork can be submitted. These generally relate to subject safety or competitive enrollment on multi-center clinical trials.
o PDs implemented without IRB approval must be submitted immediately as a protocol violation. At this time, the PI should provide an explanation for why the PD occurred without IRB approval.
Note: protocol deviations that are enrollment or participation exceptions (for one participant) do not necessarily result in changes to the protocol.
2. Complaints- Complaints may arise from different sources (subjects, researchers, health care providers, family members, etc.). Regardless of the source of the complaint, the incident should be reported to the IRB if the complaint cannot be easily resolved by the investigator or study team. All complaints received about research misconduct or noncompliance should be reported to the IRB.
Reporting Complaints:
o Complaints can be reported to the IRB on the Report Form in eIRB (Change in Protocol / For Information Form for paper protocols). Complaints may also be reported by phone or email to the IRB.
o Complaints should be taken seriously and should be reported promptly (within 24 hours) to the IRB.
3. Breach of Confidentiality- occurs when private information about a participant(s) is shared or disclosed to parties outside of the specified research personnel or as approved in the protocol. A breach of confidentiality may also occur if data are misplaced, lost or stolen.
If a breach involves Protected Health Information (PHI), the IRB will inform the SLU Privacy Officer who, in turn, will contact the investigator to evaluate the risk to participants and develop an appropriate action plan.
Reporting Breaches of Confidentiality:
o Breaches can be reported to the IRB on the Report Form in eIRB (Change in Protocol / For Information Form for paper protocols).
o Breaches may also be reported by phone or email to the IRB.
o Breaches should be taken seriously and should be reported promptly (within 24 hours) to the IRB.
o The IRB office will report any breaches of confidentiality involving PHI to the Privacy Officer.
4. Audit Notifications and Safety Reports- Research conducted at SLU is subject to audit. The IRB should receive notification of planned audits and findings of those studies that were audited. This would include any report describing an evaluation of the progress of a study, including periodic assessments of data quality and timeliness, subject recruitment, accrual and retention, participant risk versus benefit, performance of study sites, and other information that could affect study procedures and/or outcome.
Notify the IRB of any of the following:
Within 10 days
o Data Safety and Monitoring Committee reports
o FDA Safety Alerts
o FDA audits
o Other Government Agency audits (OHRP, ORI, OCR, etc.)
o Granting Agency audits (NIH, NSF, NCI, etc.)
Within 30 days (unless an issue regarding subject safety is identified)
o Sponsor and/or Contract Research Organization (CRO) Monitor Reports
Reporting Audit Notifications and Safety Reports:
o Audit Notifications and Safety Reports are to be reported to the IRB on the Report Form in eIRB (Change in Protocol / For Information Form for paper protocols).
The IRB requests that investigators notify the IRB prior to a government agency (e.g. FDA) inspection so that the IRB staff has documentation readily available if requested.
5. Subject Incarceration- refers to subjects enrolled in a SLU protocol who become prisoners.
According to 45CFR46.303, “Prisoner” means any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.
NOTE: The Office for Human Research Protections (OHRP) has indicated that probationers, parolees, persons ordered by the court to attend non-residential community programs, and individuals released from prison to halfway houses would not be considered to meet the definition of a prisoner.
Reporting Subject Incarceration:
o Subject Incarceration notifications are to be submitted to the IRB on the Report Form in eIRB (Change in Protocol / For Information Form for paper protocols).