During the conduct and oversight of human subjects research, noncompliance, unexpected adverse events, and unanticipated problems involving risks to participants or others may occur. In accordance with Brown’s IRB Policy on Mandatory Reporting, all members of the Brown community have an obligation to promptly report events related to the conduct, management, or oversight of Brown human subjects research to Brown’s Institutional Review Board/Human Research Protection Program (IRB/HRPP) for review to ensure the safety of research participants or others, uphold future research compliance, and prevent issues from reoccurring.

Additionally, research participants, their family members, or anyone else may have complaints, concerns, or questions about a Brown research study. For example, a participant may feel that they were unfairly screened out or withdrawn from a research study, that they did not receive their expected compensation, or that they were not given enough time to read the consent document before study activities began. Other complaints may include a member of the community being upset by the content of recruitment material posted near their home, or a research assistant believing that a study PI is not following the IRB-approved study protocol. Such complaints should be reported to the HRPP. All complaints or concerns reported to the HRPP are reviewed and, if necessary, further investigated.

To help with this important responsibility, this guidance document provides:

  • examples of events that must be reported;
  • glossary of key terms and their definitions.

For detailed guidance on how to promptly report these events, please refer to the following guidance documents:

  • Guidance on Submitting Reportable New Information  provides instructions for Brown researchers on how to submit Reportable New Information (RNI) related to their own approved research study through the Huron IRB Electronic Submission System and includes required reporting timeframes.


Examples of Events That Must Be Reported


The following scenarios are examples of events that may occur during conduct of a human subjects research study that must be reported to Brown’s HRPP. Some of these examples involve events that do not cause any noticeable harm to, or adverse effects on, participants or others. However, they must be reported because these events either require substantive changes to the protocol or informed consent document/process or require corrective action in order to protect the safety, welfare, or rights of participants. 

Example 1 - Stolen identifiable, sensitive information

A PI conducting behavioral research with college students collects individually-identifiable sensitive information about drug use and other illegal behaviors. The survey data are stored on a laptop computer without encryption, and the laptop computer is stolen from the PI’s car. 

Example 2 –Error handling identifiable, sensitive information

A research team member is preparing to e-mail participants a copy of their signed consent document and completed surveys detailing their demographic information, family background and medical history. The team member accidentally sends a batch e-mail of all signed consent documents and all completed surveys to all enrolled participants.

Example 3 - Negative psychological reaction to study interaction

A PI conducting behavioral research with college students involves completing a detailed survey asking questions about early childhood experiences. The IRB determined that the research involved no more than minimal risk and was approved under an expedited review category. During the completion of the survey, one student participant has a temporary psychological reaction with intense sadness and depressed mood that resolves without intervention after a few hours. The protocol and informed consent document for the research does not describe any risk of negative psychological reactions. Upon evaluation, the PI determines that the participant’s negative psychological reaction resulted from survey questions that triggered memories of physical abuse as a child. The PI had not expected that such reactions would be triggered by the survey questions.

Example 4 - Negative physical reaction to study intervention

Participants with essential hypertension are enrolled in a phase 2, non-randomized clinical trial testing a new investigational antihypertensive drug. At the time the clinical trial is initiated, there is no documented evidence of gastroesophageal reflux disease (GERD) associated with the investigational drug, and the IRB-approved protocol and informed consent document do not describe GERD as a risk of the research. Three of the first 10 participants are noted by the PI to have severe GERD symptoms that began within one week of starting the investigational drug and resolved a few days after the drug was discontinued. The PI determines that the GERD symptoms were most likely caused by the investigational drug and the informed consent document requires modification to include a description of GERD as a risk of the research.

Example 5 - Dosing error of an investigational drug

As a result of a processing error by a pharmacy technician, a participant enrolled in a multicenter clinical trial receives a dose of an investigational drug that is 10 times higher than the dose dictated by the IRB-approved protocol. While the dosing error increased the risk of toxic manifestations of the investigational drug, the participant experienced no detectable harm or adverse effect after an appropriate period of careful observation.

Example 6 – Negative physical reaction to an investigational device

A participant enrolled in a clinical trial receives a wearable investigational device. The participant is expected to wear the device for two weeks – even while sleeping and bathing. While wearing the device, the participant experiences an allergic reaction where the device comes in contact with their skin. The participant visited their primary care physician who recommended a topical anti-itch ointment and informing the study team. After learning of the situation, the PI advised the participant to stop wearing the device. The participant experienced no detectable harm or adverse effect after an appropriate period of careful observation.

Example 7 - Failure to conduct appropriate screening and testing of donors

Participants with cancer are enrolled in a phase 2 clinical trial evaluating an investigational biologic product derived from human sera. After several participants enroll and receive the investigational product, a study audit reveals that the investigational product administered was obtained from donors who were not appropriately screened and tested for several potential viral contaminants, including HIV and hepatitis B.

Example 8 - Increased frequency of emergency surgery due to the study intervention

Participants with coronary artery disease presenting with unstable angina are enrolled in a multicenter clinical trial evaluating the safety and efficacy of an investigational vascular stent. Based on prior studies in animals and humans, the research team anticipates that up to 5% of participants receiving the investigational stent will require emergency coronary artery bypass graft (CABG) surgery because of acute blockage of the stent that is unresponsive to non-surgical interventions. The risk of needing emergency CABG surgery is described in the IRB-approved protocol and informed consent document. After the first 20 participants enrolled in the study, a data safety monitoring board (DSMB) conducts an interim analysis, as required by the IRB-approved protocol, and notes that 10 participants needed to undergo emergency CABG surgery soon after placement of the investigational stent. The DSMB concludes that the rate at which participants needed to undergo CABG greatly exceeds the expected rate and communicates this information to investigators.

Example 9 - Acute effects from a study drug not described in the drug’s risk profile

A participant develops severe hepatic failure complicated by encephalopathy one month after enrolling in a phase 2, open-label, uncontrolled clinical study and starting the new, oral biologic under evaluation for treatment of severe psoriasis unresponsive to FDA-approved treatments. The known risk profile of the new, oral biologic prior to this event included mild elevation of serum liver enzymes in 10% of participants receiving the biologic during previous clinical studies, and there was no other history of participants developing clinically-significant liver disease. The IRB-approved protocol and informed consent document for the study identifies mild liver injury as a risk of the research. The investigators identify no other etiology for the liver failure in this participant and attribute it to the study biologic.

Glossary and Definitions

Adverse Event (AE): Any untoward or unfavorable occurrence (physical or psychological) in a human participant, including any abnormal sign, symptom, or disease, temporally associated with the participant’s time in a research study, whether or not considered related to their participation. These events can occur in the context of biomedical or social/behavioral research. This term is construed broadly.

Continuing Noncompliance: Any demonstrated pattern of noncompliance that may indicate (i) an insufficient  understanding or misapplication of federal, state, or local regulations that govern human subjects research, or institutional polies and procedures that apply to human subjects research; (ii) a compromise of the study quality or scientific integrity such that important conclusions can no longer be reached; or (iii) frequent instances of noncompliance suggesting a likelihood that noncompliance will continue without intervention.

Minimal Risk (non-incarcerated populations): Probability (likelihood) and magnitude (consequences) of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

Minimal Risk (incarcerated populations only): Probability (likelihood) and magnitude (consequences) of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.

Noncompliance: Includes, but is not limited to, any incident involving (i) a failure to comply with federal, state, or local regulation that governs human subjects research; (ii) a violation of institutional policies or procedures applicable to human subjects research; (iii) any unapproved deviation from stipulations imposed by the institution as a condition of IRB/HRPP approval; and (iv) any unapproved deviation from an IRB/HRPP-approved protocol, unless such deviation is necessary to preserve the life or health of a participant and the IRB/HRPP is notified as soon as possible after the deviation occurs.

Related or Possibly Related to Participation: An adverse event may be related or possibly related if there is a reasonable possibility that the incident, experience, or outcome may have been caused by the research activities.

Serious Adverse Event (SAE): Any adverse event that (i) results in death; (ii) is life-threatening (places the subject at immediate risk of death from the event as it occurred); (iii) results in inpatient hospitalization or prolongation of existing hospitalization; (iv) results in persistent or significant disability/incapacity; (v) results in congenital anomaly/birth defect; or (vi) based upon appropriate medical judgement, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

Serious Noncompliance: Any incident of noncompliance that involves a willful disregard or knowing violation of the federal, state, or local regulations that governs human subjects research, or the institutional policies and procedures that apply to human subjects research, which may have included or led to a (i) significant harm, or a risk of significant harm, to the rights, welfare, or safety of participants; or (ii) significant compromise of the quality or scientific integrity of a human subjects research study.

Suggests Research Places Participants or Others at a Greater Risk of Harm than Previously Known: An adverse event may suggest the research places participants or others at a greater risk of harm than previously known or recognized based on the information available at the time of IRB approval or new information revealed while the study is underway. The risk of harm include, but is not limited to, physical, psychological, economic, or social harm.

Suspension: An action taken by convened IRB, the IRB Chair, a federal agency, sponsor, or sponsor-investigator to temporarily stop some or all approved research activities in order to protect participants pending completion of an investigation. Suspended studies remain open until the convened IRB or applicable federal agency determines to (i) lift the suspension or (ii) terminate the study or some activities of the study.

Termination: An action taken by the convened IRB, the IRB Chair, a federal agency, sponsor, or sponsor-investigator to permanently stop all research activities in an approved research study.

Unanticipated Adverse Device Effects: Any serious adverse effect on health or safety, 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 FDA Investigational Device Exemption application; or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

Unanticipated Problem Involving Risks to Participants or Others: Any incident, experience, or outcome in the course of human subjects research that is (1) unexpected (in terms of nature, severity, or frequency), (2) related or possibly related to participation in research, and (3) suggests that the research places participants or others at greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Unexpected: An adverse event may be unexpected (in terms of nature, severity, or frequency) given the research procedures described in the IRB-approved study documents, and the characteristics of the enrolled participant population.

Unexpected Adverse Event: Any adverse event (AE) occurring in one or more participants in a research study, the nature, severity, or frequency of which (i) is not considered consistent with either the known or foreseeable risk of AEs associated with the procedures involved in the research that are described in the protocol-related documents, investigator brochure, informed consent document, or other relevant sources of information regarding the research, such as product or device labeling and package inserts; or (ii) is not considered consistent with the expected natural progression of any underlying disease, disorder, or condition of the participant(s) experiencing the AE and the participant’s predisposing risk factor profile for the AE.