During the course of the research, investigators may encounter certain types of occurrences or situations such as unanticipated problems or adverse events, protocol deviations and protocol violations, which investigators must report to the IRB.
Please note that the guidance below is for reporting to the IRB only and does not satisfy required reporting by an investigator (professional or student) to other internal or external oversight bodies or departments (e.g. NSF/NIH, the FDA, Other External Sponsors, RU Compliance Office, DSMB, or Privacy Offices).
Principal Investigator's Responsibilities
Federal regulations [45 CFR 46.103(b)(5) and 21 CFR 56.108(b)(1)] require the IRB to ensure that investigators promptly report “any unanticipated problems” or adverse events. An essential element of human subjects protection is identifying, analyzing the causes of, and responding appropriately to expected and unexpected adverse events, as well as unanticipated problems involving risks to subjects or others. Investigators are required to identify and help analyze the events and to determine any appropriate changes or to formulate responses to such events. In addition, investigators must inform the IRB promptly of all such events and/or protocol deviations as described below. The IRB is required to make independent judgments concerning the significance of events and information in the context of the research project and the need for changes to the study protocol and/or informed consent process to protect research subjects.
Investigators and their designated research staff are responsible for reporting information concerning the approved research to the IRB in a timely fashion, understanding and adhering to the reporting guidance provided here and on the detail pages linked below, and not implementing any changes to the research prior to IRB approval of the change via an amendment. The ONLY exception to this policy is when an unanticipated event occurs in a study that could lead to imminent harm to the subject [45 CFR 46.103(b)(4)(iii) and 21 CFR 56.108(a)(4)].
Federal Regulations requires the Principal Investigator to report any unanticipated problems, protocol deviations and/or violations on their IRB-approved protocol to their respective IRB. Rutgers IRB requires the Rutgers Investigator to report such incidents to:
- Rutgers IRB using the appropriate form within the deadlines as described;
- Study Funders/Sponsors, RU Compliance Office etc, where applicable;
The Principal Investigator must notify the IRB according to the following timelines:
- Study-related death or Serious Adverse Event: 24 hours;
- Other Unanticipated Problems or Adverse Events: 5 business days - from date of discovery;
- Protocol Deviations/Violations: 5 business days - from date of discovery;
- Anticipated Problems:
- Expedited/FB Studies: Include with next Continuing Review;
- Exempt Studies: Contact the IRB for additional guidance;
NOTE: If it is the opinion of the Principal Investigator that a fatal or life-threatening event is likely related to the protocol, then all research activity should stop until the IRB has reviewed the adverse event and consulted with the Principal Investigator. If only one or two of the above criteria have been met, you do not have to report the event; however, if you are unsure whether an event qualifies as a reportable event, it is recommended that you report it.
Types of Reportable Events
Unanticipated Problems and/or Adverse Events
An Unanticipated problem is any problem or event which in the opinion of the local investigator was unanticipated, reflects new or increased risk to the subjects and was possibly related to the research procedures.
An Adverse Event is defined as: (1) any medical, physiological, psychological, behavioral, social or economic event that is undesirable and unintended, although not necessarily unexpected; (2) an event in which the outcome is fatal or life threatening, causes permanent disability, causes hospitalization or prolongation of hospitalization; (3) an overdose; or (4) a complaint by a research subject or family member of a research subject concerning the research or the protocol. Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research (modified from the definition of adverse events in the 1996 International Conference on Harmonization E-6 Guidelines for Good Clinical Practice). Adverse events encompass both physical and psychological harms. They occur most commonly in the context of biomedical research, although on occasion, they can occur in the context of social and behavioral research.
Examples of Unanticipated Problems or Adverse Events
- Project involves recorded interviews with married couples, which the recordings include identifiable information, and the recording device is stolen/lost. The investigator must file an adverse event form with the IRB, including any actions taken to address the event.
- Study involves depression treatment for adolescents and a minor subject reports suicidal ideation during a therapeutic session to study staff. The investigator must address this situation in a time-sensitive fashion plus report this to the parents and to the appropriate authorities. In addition, the investigator must file an adverse event form to the IRB.
*intended as a guide and not all-inclusive list;
An Unanticipated Problem or Adverse Event is an event that meets all three of the following criteria:
- It is unexpected in terms of nature, severity or frequency, given the research protocol, investigator’s brochure, IRB-approved informed consent document, product labeling and other sources of information, and given the characteristics of the subject population being studied(expected natural progression of subjects’ disease, disorder or condition or predisposing risk factor profiles);
- It is related or possibly related to participation in the research (i.e. is there a definite or reasonable possibility that the incident, experience or outcome may have been caused by the research drug/device or research procedures) ; and
- The event suggests that the research potentially places subjects or others at a greater risk of harm (including physical, psychological, economic or social harm) than was previously known or recognized).
The IRB notes that an incident, experience, or outcome that meets the three criteria above generally will warrant consideration of substantive changes in the research protocol or informed consent process/document or other corrective actions in order to protect the safety, welfare, or rights of subjects or others.
NOTE: Anticipated Problems which are already described as potential risks in the consent form (i.e., Consent mentioned that risks include experimental therapy might not be effective at controlling subject’s underlying condition. For example, subject with depression is participating on a intervention protocol and becomes hospitalized for flare-up of depression symptoms) and/or Unrelated Events (e.g., subject is injured in a car accident and misses their scheduled study session) do not meet the above definition and should only be reported in summary form to the IRB at time of continuing review. However, a study sponsor/funder (e.g., NIH/NSF) might require investigators to report this problem/event to them in a separate process of which the investigator must seek guidance directly from their study sponsor/funder.
Protocol Deviations and/or Protocol Violations
A protocol deviation is any change, divergence, or departure from the study design or procedures of a research protocol that is under the investigator's control and that has not been approved by the IRB. Upon discovery, the Principal Investigator is responsible for reporting protocol deviations to the IRB.
A protocol violation is a deviation from the IRB approved protocol that may affect the subject's rights, safety, or well-being and/or the completeness, accuracy and reliability of the study data. Protocol Violations must be submitted for Full Board IRB review. If the deviation meets any of the following criteria, it is considered a protocol violation.
Protocol deviations and protocol violations can be broken down into the following two categories: Minor deviation or violation OR Major deviation or violation.
- Minor Deviations and/or Minor Violations: A minor deviation or minor violation is viewed by the IRB as an event that does not impact subject safety, compromise the integrity of study data and/or affect a subject’s willingness to participate in the study. Minor deviations or violations will be reviewed under expedited procedures by a single reviewer. The reviewer will determine whether the event is accepted as a minor deviation/violation and can recommend a corrective course of action. The deviation will be sent to the fully convened IRB meeting where the board will discuss and determine if any additional actions are required, where applicable and as necessary. If the event meets any of the following criteria, it is considered a minor deviation or minor violation: Examples (Minor)
- Major Deviations and/or Major Violations: A major deviation or violation is viewed by the IRB as an event that may impact subject safety, affect the integrity of study data and/or affect a subject’s willingness to participate in the study. Major protocol deviations/violations are treated as noncompliance. These reports will be reviewed at the fully convened IRB meeting where the board will discuss the major deviations and/or major violations and determine of the appropriate course of action. If the event meets any of the following criteria, it is considered a major deviation or major violation: Examples (Major)
Acknowledgement of Reportable Events by the IRB
Once a Principal Investigator submits a report concerning a reportable event, the Rutgers IRB will send the report to the fully convened meeting for review. Rutgers IRB will follow up with the PI before or after the meeting regarding any appropriate changes or any next steps. Once an event is acknowledged, the Principal Investigator will receive an "Acknowledgement Letter" via e-mail from the Rutgers IRB. The Principal Investigator is responsible for communicating any IRB-required actions, changes or acknowledgements with study staff and/or study sponsors.
Another Type of Reportable Event: Data & Safety Monitoring Reports
Data and safety monitoring is used to ensure both adherence to the IRB-approved investigative plan, the validity of data collected and most importantly, the safety of those subjects who participate in the project. A data monitoring plan might be required for projects that involve investigation items/devices or are clinical trials, no matter the risk level. Data and safety monitoring usually occurs with the formation of a Data and Safety Monitoring Board (DSMB). The DSMB is an independent group of experts that advises the principal investigator and if applicable any co-Investigators. For More Detailed Information on DSMBs
HealthSci (New Brunswick and Newark)