DHHS and FDA regulations require prompt reporting to the IRB, appropriate IO, and appropriate federal departments or agency heads of 1) unanticipated problems involving risk to participants or others, 2) any serious or continuing noncompliance with regulations or the requirements of the IRB, and 3) any suspension or terminations of IRB approval.
It is the responsibility of the PI to assess events that occur during the course of a research protocol, and determine which of the following descriptions apply. The IRB will review reports and make a final determination, indicating agreement or disagreement with the PI’s assessment, and why.
An Adverse Event is an event that occurs during the course of a research protocol that either causes physical or psychological harm, or increases the risk of physical or psychological harm, or results in a loss of privacy and/or confidentiality to a research participant or others (such as family members).
An Anticipated Adverse Event is one that is reasonably expected and/or listed in the protocol and consent form as a risk of participating in the research. Examples of an anticipated adverse event include, but are not limited to, the following:
- A participant in an exercise physiology study experiences muscle strain following an exercise session;
- A participant in a study with blood draws experiences light headedness or fainting during the blood drawing process;
- A participant in a study of post-traumatic stress syndrome becomes upset during the re-telling of the traumatic event and requires a referral to a counselor.
An Unanticipated Adverse Event is one that was not reasonably expected and/or is not listed in the protocol and consent form as a risk of participating in the research. Examples of an unanticipated adverse event include, but are not limited to, the following:
- A participant in a study of the benefits of eating strawberries experiences a previously undetected allergy to strawberries;
- A child participant in a study of how to improve classroom behavior experiences bullying by other students as a result of her participation in the study.
A Serious Adverse Event is one whose magnitude or frequency is above expectation. For example:
- Previous research data indicates that the expected rate of an injury from a certain interventional procedure is 1 in 1000, but the same procedure used in a protocol under review has a much higher rate (e.g., 1 in 100);
- An anticipated side effect of a certain dietary protocol results in a much more serious manifestation of that effect than would be expected (i.e., a high-fiber diet results in severe diarrhea and vomiting requiring hospitalization).
A Related adverse event is one that, in the opinion of the investigator, is likely caused by or affects the research.
- A participant in a study about post-traumatic stress disorder experiences a panic attack after telling the investigator about a incidence of childhood sexual abuse;
- A participant in a study about the benefits of a nutritional supplement on recovery from weight lifting experiences an allergic reaction to the product after it is ingested.
Events that are not related to study procedures and are not serious may be reported at the time of re-approval. Examples of unrelated events that may be reported at the time of re-approval include:
- A participant in a study gets the flu and has to withdraw from the study (report as a withdrawal);
- A participant in a longitudinal study of high school students’ transition to college life drops out of school and withdraws from the study (report as a withdrawal);
- A participant in an observational study of child behavior during recess falls on the playground and sprains her ankle (report in summary of findings);
- A participant in a study on the benefits of eating carrots on eyesight reports an incident of food poisoning from eating out at a restaurant and has to miss one of six scheduled visits to the laboratory. The protocol should accommodate for missed session make-ups.If not, this would be reported as a protocol deviation (missed session) but not as an adverse event (food poisoning unrelated to study procedures).
Examples of serious and related adverse events are:
- The death of a research participant due to research procedure(s);
- Any change to the protocol made without prior IRB review to eliminate apparent immediate hazard to a research participant or others;
- Any event that requires prompt reporting according to the protocol or the study sponsor;
- A serious breach of privacy or confidentiality of research participants or others (such as family members);
- Any publication in the literature, safety monitoring report, interim result, or other finding that indicates an unexpected change to the risks or potential benefits of the research;
- Any complaint of a participant that indicates an unanticipated risk or which cannot be resolved by the research staff;
- Any other event or other problem which, in the opinion of the PI, was (1) previously unforeseen and (2) presents risks to research participants or others.
Reporting of Adverse Events
Using the Adverse Event Report Form (IRB-4), PIs are required to report to the IRB serious and related events no later than 2 working days after discovery of their occurrence. Events that are not related to study procedures and are not serious may be reported at the time of re-approval. All other events must be reported within 5 working days after discovery of their occurrence. This policy applies to events that occur at UConn or at an off-campus study site.
Unanticipated Problems, Protocol Deviations and Noncompliance
An Unanticipated Problem is defined as any unforeseen event that involves risk to the participant or others that is related to either a research intervention or interaction, or the conduct of the study in general. Examples of unanticipated problems involving risk include, but are not limited to, the following:
- an accidental or unintentional change to the IRB-approved protocol (e.g., the software program for an on-line survey study about college students’ use of illegal drugs has a glitch that enables research participants to view other participants’ identifiable survey responses);
- a complaint from a participant that indicates an unanticipated risk (e.g., loss of employment due to disclosure of data, etc.);
- unexpected changes to the risk/benefit profile of the study (e.g., based on literature, safety reports, interim results or other findings);
- unforeseen events involving the research team (e.g., the loss of a laptop computer with identifiable participant information, sudden unavailability of the PI and/or co-investigator, etc.);
- unexpected serious adverse events (internal or external) that in the opinion of the PI may be related to the study intervention;
- any change to the protocol taken without prior IRB review to eliminate apparent immediate hazard to a research participant when the immediate hazard is, in the opinion of the PI, related to the study.
Protocol Deviations and Noncompliance are defined as any action that is taken or occurs that is not in accordance with an IRB approved study, IRB policies or regulations, or failure to follow the requirements and determinations of the IRB. Protocol deviations and noncompliance may be minor (e.g., a participant is one day late for a study visit due to a family emergency and there is no impact on the safety of the participant due to the late visit), or may be considered serious or continuing.
Examples of protocol deviations include equipment failures during study procedures, the use of the wrong version of a form (including unvalidated consent forms), and enrolling study participants who do not meet the approved inclusion criteria.
Noncompliance and protocol deviations are considered serious when they create increased risks to participants, adversely affect the rights and welfare of participants, or affect the scientific integrity of a study. Willful violations of IRB policies and/or Federal regulations, including those pertaining to obtaining informed consent, reporting of adverse events, and disclosure to participants of conflicts of interests and risks associated with a study, are also considered examples of serious noncompliance.
Noncompliance is considered to be continuing noncompliance when a pattern of noncompliance exists that, if allowed to continue, is likely to increase risks to participants, adversely affect the rights and welfare of participants, or affect the scientific integrity of the study. It may involve the same mistake being made repeatedly within one study or across studies (e.g., a co-investigator on two of the PI’s approved studies fails to document participant consent) or the same mistake being made after a corrective plan has been issued to the investigator for previous findings of noncompliance. The IRB will make the final determination as to what constitutes continuing noncompliance.
Reporting Unanticipated Problems, Protocol Deviations and Noncompliance
Unanticipated problems are to be reported to the IRB using the Adverse Event Report Form (IRB-4) and must be reported within 5 working days after discovery of their occurrence. This policy applies to events that occur at UConn or at an off-campus study site. The IRB will make the final determination as to whether an incident constitutes an unanticipated problem. Noncompliance and protocol deviations are to be reported to the IRB using the Protocol Deviation Report Form (IRB-6) and must be reported within 5 working days after discovery of their occurrence. The IRB will make the final determination as to whether an incident constitutes serious noncompliance.