During the course of a research study, unanticipated problems involving risk to subjects or others, non-compliances, and other events may occur that need to be reported to the IRB in accordance with 45 CFR.46.103(b)(5) and 21 CFR 56.108(b). The list below is intended to help ensure that the reporting and review of these events occur in a timely, meaningful way so that research participants can be protected from avoidable harms.
Report the information items that fall into one or more of the following categories to the IRB within 5 business days using theelectronic IRB (eIRB). For any questions or clarifications on the below, please call the IRB office at 617-636-7512:
Information items can be reported to the IRB using the eIRB in one of two ways:
Go to the main IRB page and select the Report New Information button on the left side. This way, if an information item applies to multiple studies, you can link it to each individual study by adding each study in the smartform under Question 6. Related studies and modifications.
Go into the study workspace for the individual study and select the Report New Information button from there. You can still add other studies to this information item under Question 6. Related studies and modifications if the information item also applies to other studies.
Information that does not fall under any of the categories does not require reporting to the IRB.
Information that indicates a new or increased risk, or a new safety issue. For example:
New information (e.g., an interim analysis, safety monitoring report, publication in the literature, sponsor report, or investigator finding) indicates an increase in the frequency or magnitude of a previously known risk, or uncovers a new risk.
An investigator brochure, package insert, or device labeling is revised to indicate an increase in the frequency or magnitude of a previously known risk, or to describe a new risk.
Withdrawal, restriction, or modification of a marketed approval of a drug, device, or biologic used in a research protocol.
Protocol violation that harmed subjects or others or that indicates subjects or others might be at increased risk of harm.
Complaint of a subject that indicates subjects or others might be at increased risk of harm or at risk of a new harm
Any changes significantly affecting the conduct of the research
Harm: Any harm experienced by a subject or other individual that, in the opinion of the investigator, is unexpected and at least probably related to the research procedures.
A harm is “unexpected” when its specificity or severity is inconsistent with risk information previously reviewed and approved by the IRB in terms of nature, severity, frequency, and characteristics of the study population.
A harm is “probably related” to the research procedures if, in the opinion of the investigator, the research procedures more likely than not caused the harm.
Non-compliance: Non-compliance with the federal regulations governing human research or with the requirements or determinations of the IRB, or an allegation of such non-compliance.
Audit: Audit, inspection, or inquiry by a federal agency.
Report: Written reports of study monitors.
Researcher error: Failure to follow the protocol due to the action or inaction of the investigator or research staff.
Confidentiality: Breach of confidentiality.
Unreviewed change: Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a subject.
Incarceration: Incarceration of a subject in a study not approved by the IRB to involve prisoners.
Complaint: Complaint of a subject that cannot be resolved by the research team.
Suspension: Premature suspension or termination of the research by the sponsor, investigator, or institution.
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.
Reminder about removing identifiers (name, MR#, etc.)
Do not include subject identifiers when submitting reportable new information to the IRB, unless identifying the subject is absolutely necessary (for example, if the IRB will need to contact the subject).
In general, when submitting reportable new information, redact subject identifiers by doing the following:
Make a copy of the document
Using a black marker, black out the subject’s name and any other subject identifiers, then
Photocopy this redacted (blacked out) copy so the identifiers cannot be read through the black marker
When corresponding by e-mail, re-read your e-mail to double check that the e-mail and any e-mails in the chain do not include subject identifiers.
Adverse Event: 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).
External Adverse Event: From the perspective of one particular institution engaged in a multicenter clinical trial, external adverse events are those adverse events experienced by subjects enrolled by investigators at other institutions engaged in the clinical trial.
Internal Adverse Event: From the perspective of one particular institution engaged in a multicenter clinical trial, internal adverse events are those adverse events experienced by subjects enrolled by the investigator(s) at that institution. In the context of a single-center clinical trial, all adverse events would be considered internal adverse events.
Possibly Related to the Research: There is a reasonable possibility that the adverse event, incident, experience or outcome may have been caused by the procedures involved in the research (modified from the definition of associated with use of the drug in FDA regulations at 21 CFR 312.32(a)).
Serious Adverse Event: Any adverse event temporally associated with the subject’s participation in research that meets any of the following criteria:
results in death;
is life-threatening (places the subject at immediate risk of death from the event as it occurred);
requires inpatient hospitalization or prolongation of existing hospitalization;
results in a persistent or significant disability/incapacity;
results in a congenital anomaly/birth defect; or
any other adverse event that, based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (examples of such events include allergic bronchospasm requiring intensive treatment in the 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).
(Modified from the definition of serious adverse drug experience in FDA regulations at 21 CFR 312.32(a).)
Unanticipated problem involving risks to subjects or others: Any information, including any incident, experience, or outcome that meets ALL of the following conditions:
Unexpected (in terms of nature, severity, or frequency) given the procedures described in the research protocol documents (e.g., the IRB-approved research protocol and informed consent document) and the characteristics of the human subject population being studied;
Related or possibly related to participation in the research (“possibly related” means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
Suggests that the research places human subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized, even if no harm has actually occurred.
Unexpected adverse event: Any adverse event occurring in one or more subjects in a research protocol, the nature, severity, or frequency of which is not consistent with either:
the known or foreseeable risk of adverse events associated with the procedures involved in the research that are described in (a) the protocol–related documents, such as the IRB-approved research protocol, any applicable investigator brochure, and the current IRB-approved informed consent document, and (b) other relevant sources of information, such as product labeling and package inserts; or
the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event.
(Modified from the definition of unexpected adverse drug experience in FDA regulations at 21 CFR 312.32(a).)