1.0 Policy Purpose
The purpose of this policy is to describe the process and responsibilities for reporting and reviewing events that meet reporting criteria and occur in the context of a human subjects research study approved by the Brown University Institutional Review Board (IRB) or Human Research Protection Program (HRPP).
2.0 To Whom the Policy Applies
This Policy applies to Research Personnel, including Principal Investigators (PIs), of human subjects research studies approved by the Brown IRB or HRPP.
3.0 Policy Statement
The Brown IRB and HRPP are committed to ensuring that Research Personnel timely report certain types of events that occur in the conduct of human subjects research to enable the IRB/HRPP to evaluate the event, the research team’s response, the proposed corrective action plan, and report the event, when required, to federal agencies or others. This Policy defines the processes for reviewing and reporting Reportable Events, including Unanticipated Problems Involving Risks to Subjects or Others (UP); Unexpected Adverse Events Related to the Research (UAE); Continuing Noncompliance and Serious Noncompliance; and Suspensions or Terminations to the Institutional Official (IO) and/or federal department or agency heads.
3.1 Reportable Events
Principal Investigators must report to Brown’s HRPP the occurrence of any of the events described below, collectively referred to as Reportable Events:
- Any Adverse Event (AE) that (1) is a UAE and (2) is related or possibly related to participation in the research.
- Any UP.
- Any breach of Privacy or Confidentiality, including lost or stolen confidential information of a research participant.
- Any medical, procedural, or laboratory error potentially increasing risk to participants (e.g., errors in drug administration or dosing, surgical or other procedures, testing of samples, or test results).
- Any interim analysis, safety monitoring report, publication in a peer-reviewed journal, or other finding indicating that there are new or increased risks to subjects or others, or that subjects are less likely to receive any direct benefits from the research study than as initially presented to the IRB or HRPP.
- Any complaint by or on behalf of a subject indicating that the rights, welfare, or safety of the subject have been adversely affected.
- Any change in the Food and Drug Administration (FDA) labeling; any change in the status of an Investigational New Drug Application (IND) or Investigational Device Exemption (IDE); any withdrawal from market; any manufacturer alert from the sponsor of the research study; or any recall of an FDA-approved drug, device, or biologic under investigation in the research study.
- Any event that requires prompt reporting to the sponsor of the research study, when applicable.
- A Suspension or Termination of a research study or of a study’s enrollment, including by the FDA or the sponsor of the research study, based on information indicating that the research study places subjects at an increased risk of harm than was previously known or recognized.
- Any other event that is unanticipated (irrespective of any “relatedness” to the research) and indicates that the research study places subjects or others (e.g., other investigators, research assistants, students, the public, family members or partners of subjects) at an increased risk of harm or otherwise adversely affects the rights, welfare, or safety of subjects or others.
Brown University considers Minor Protocol Deviations to meet the definition of Noncompliance, and as such Minor Protocol Deviations are distinct from Reportable Events.
Multiple Minor Protocol Deviations related to an approved protocol may be determined by the Brown IRB to constitute Continuing Noncompliance; if so, the IRB or HRPP may instruct the PI to submit the Continuing Noncompliance as a Reportable Event.
3.3 Reporting Timeframes
Principal Investigators must report Reportable Events to the HRPP in accordance with the following timeframes:
- Reportable Events that are either life-threatening or have resulted in death must be reported to the HRPP via telephone, or email if phone is not possible, within one business day from the date the PI is notified of or discovers the Reportable Event. The PI must ensure that Research Personnel are trained to report any Reportable Event to the PI promptly upon discovery, and no later than 24 hours following its discovery or occurrence. A Reportable Events Form must be submitted to the HRPP within 48 hours of the PI’s initial verbal or email notification to the HRPP of the Reportable Event.
- Reportable Events that are not life-threatening and have not resulted in death must be reported to the HRPP in writing as soon as possible, and no later than 7 business days from the date the PI is notified of or discovers the Reportable Event.
- Minor Protocol Deviations must be reported to the HRPP in writing at the time of continuing review when continuing review is applicable to the study protocol, and must be reported during any quality assurance/quality improvement assessment by the HRPP. If continuing review is not applicable to the study protocol, the PI must maintain Minor Protocol Deviations as part of the study record and make the study record available upon request to the IRB, HRPP, and/or any federal sponsor or regulatory agency, as applicable.
3.4 Reporting Reportable Events
In accordance with the timeframes outlined above, PIs must submit to the HRPP a Reportable Events Form and include the following information:
- Identifying information for the research study, including the study title, the PI’s name, and the IRB protocol number;
- A detailed description of the Reportable Event, including relevant dates and times;
- A detailed description of any corrective action or change to the protocol, planned or already taken, to ensure that the Reportable Event is corrected and will not occur again;
- An assessment of whether any research participants or others were placed at risk as a result of the Reportable Event, or suffered any physical, social, or psychological harm and any plan to address these consequences; and
- Any other information deemed relevant by the PI
For multisite research studies, if Brown is the IRB of record and the event could occur at other study sites, the Brown PI must ensure that any other sites also implement such proposed changes to the protocol or to the informed consent document in response to a Reportable Event. If Brown has ceded IRB oversight to another institution, the Brown PI is expected to follow the reporting requirements and policies of the IRB of record.
3.5 Review of Reportable Events
Once received, the HRPP will review the completed Reportable Events Form to ensure it meets the defined reporting criteria, then forward it to the IRB Chair. (For purposes of this policy, “IRB Chair” refers to the IRB Chair or the IRB Chair’s designee(s) as documented by delegated signature and approval authority).
Within 10 business days of receiving the report, the HRPP will inform the PI whether any additional information, actions, or reporting is required of the PI or other parties. The IRB Chair has the authority to require, as a condition of continued approval by the IRB, submission of more detailed information by the PI, the sponsor of the research study, or others, about any Reportable Event occurring in a research study.
Upon review of the Reportable Events Form, the IRB Chair may take one or more of the following actions:
- Acknowledge the Reportable Event. The HRPP will retain the associated Reportable Events Form as part of the IRB’s records without further review.
- Accept the Reportable Events Form and approve the proposed changes, if any, with no further action required.
- Require additional information related to the Reportable Event from the PI and/or others.
- Require modifications to the study and/or informed consent documents.
- Require that current subjects be provided with information regarding the Reportable Event or other information (e.g., if the information may relate to research participants’ willingness to continue participation).
- Require that research participants who previously participated in the research study be informed of the Reportable Event.
- Require that current participants be re-consented if the Reportable Event identifies new or increased risks than previously known.
- Require that the PI and/or Research Personnel complete additional training.
- Request an audit of the research by Brown University’s Office of Research Integrity (ORI).
- Suspend the research.
- Terminate the research.
- Refer the Reportable Event for review at a Convened IRB meeting (i) if the IRB Chair determines that the changes to the research study in response to the Reportable Event are more than minimal, or (ii) at the discretion of the IRB Chair.
- Require any other actions deemed appropriate by the IRB Chair.
If the IRB Chair refers the event for review at a Convened IRB meeting, the IRB, by majority vote of a quorum of the members present at the convened meeting, may take one or more of the actions listed above.
For multisite research studies, if the IRB Chair proposes changes to the study or consent document(s) in addition to those proposed by the sponsor of the research study, the coordinating center, or the PI, the IRB Chair should request in writing that the PI discuss the proposed revisions with the sponsor of the research study or the coordinating center and submit a response or necessary changes for review by the IRB Chair.
3.5.1 Review of Unanticipated Problems Involving Risks to Subjects or Others
The IRB Chair will determine whether the Reportable Event constitutes an UP. If the Reportable Event constitutes an UP, further reporting to the IO and, when applicable, sponsoring agency is required.
The IRB Chair will notify the PI in writing of the findings related to the Reportable Event, and will send copies of the findings to the Chair of the PI’s department and/or research unit. Such notice will inform the PI that the PI has 10 business days from receipt of the notice to request reconsideration of the IRB Chair’s decision. To request reconsideration, the PI must send the IRB a written request for reconsideration that includes the basis for the request. Once submitted, the IRB Chair will bring the request to the next Convened IRB meeting, as appropriate, and the full IRB will make a determination whether to uphold, reverse, or revise the IRB Chair’s decision. This determination is final and cannot be appealed or reconsidered. The HRPP will notify the PI of the final outcome.
3.6 Serious Noncompliance by Research Personnel
All Research Personnel must conduct human subjects research with the highest degree of integrity and in compliance with federal and state requirements, sponsor requirements, and Brown policies, as well as in accordance with the corresponding human subjects research protocol. Research Personnel have a responsibility to report incidences of Serious Noncompliance conducted willfully discovered or observed in a human subjects research study approved by the Brown IRB or HRPP.
3.6.1 Documenting an Allegation of Serious Noncompliance
Reports of an Allegation of Serious Noncompliance conducted willfully by Research Personnel must be made in writing to at least one of the following individuals: the IRB Chair, the HRPP Associate Director, or the Senior Director of ORI. If the individual reporting a Serious Noncompliance (the complainant) prefers to report anonymously, the individual may do so via Brown’s Anonymous Reporting Hotline.
An Allegation of Serious Noncompliance must be raised in good faith, be made in writing, and include a complete description of the Serious Noncompliance, the observed circumstances, and the names of the individuals involved. The report must contain sufficient details to allow an assessment of the Serious Noncompliance. An Allegation of Serious Noncompliance must be reported as soon as possible after it is observed or discovered.
Only under extenuating circumstances in which a written report is infeasible may an Allegation of Serious Noncompliance be made verbally to the IRB Chair, the HRPP Associate Director, or the Senior Director of ORI. The individual receiving a verbal report of an Allegation of Serious Noncompliance is responsible for creating a written account of the report. The complainant must review the written account and affirm in writing that the Allegations of Noncompliance are accurate and complete as transcribed.
The identity of the individual making an Allegation of Serious Noncompliance will be kept confidential upon a request made by that individual and to the extent possible, when the complainant makes a report in good faith. This protection will hold even if the Allegation of Serious Noncompliance is found, upon investigation, to be without merit.
3.6.2 Preliminary Assessment of an Allegation of Serious Noncompliance
Once an Allegation of Serious Noncompliance is received, the IRB Chair, the HRPP Associate Director, and the Senior Director of ORI (collectively, the Review Panel) will conduct a preliminary review of the Allegation of Serious Noncompliance and any other documents relevant to the study and/or the potential Serious Noncompliance. If any member of the Review Panel cannot conduct or participate in a preliminary review for any reason, including conflict of interest, the Vice President for Research will designate an individual to replace the Panel member for purposes of that specific preliminary review. If necessary to better ascertain the nature and scope of the Allegation of Serious Noncompliance, the Review Panel may request an audit of the research study, interview Research Personnel, or take whatever other actions deemed necessary to assess the Allegation of Serious Noncompliance.
Following the preliminary review by the Review Panel, the Senior Director of ORI (or that person’s replacement on the Panel) may refer the Allegation to other University Boards, Committees, or individuals for assessment if some or all of the Allegation(s) fall under the purview of another University policy.
The Review Panel will make a determination as to whether there is support for a finding of Serious Noncompliance.
- If the facts do not support a finding of willful, Serious Noncompliance, as determined by the individuals reviewing the Allegation as part of the preliminary assessment, the Allegations of Serious Noncompliance may be dismissed and no further action is required.
- If the facts support a finding of willful, Serious Noncompliance, as determined by the individuals reviewing the Allegation, the matter will be referred to the Convened IRB for further review.
Regardless of the finding, a written report of the preliminary assessment and the determination made by the individuals reviewing the Allegation will be retained in the Office of Research Integrity.
If, at any point during the preliminary assessment, the individuals reviewing the Allegation, determine in their sole discretion that an Allegation warrants the Suspension or Termination of the research to ensure protection of the rights and welfare of research subjects, the individuals reviewing the Allegation may invoke appropriate procedures to suspend or terminate the research.
3.6.3 Considerations by the IRB
The IRB will review an Allegation referred to it by the Review Panel and any other documents relevant to the study and/or the potential Serious Noncompliance. The IRB may, at its discretion, consider new or additional information not considered by the Review Panel. The IRB may also appoint a subcommittee to further investigate the Allegation and to make recommendations to the IRB.
220.127.116.11 Actions with Respect to the Human Subject Research Protocol
After considering the Allegation, the IRB may take one or more of the following actions with respect to the human subjects research protocol:
- Approve the research to continue with no further action required;
- Defer action pending additional information;
- Require modifications to the study and/or consent documents;
- Require that current subjects be provided with information regarding the Noncompliance or of other relevant information;
- Require that current participants be re-consented or notified in writing of the Noncompliance or of other relevant information;
- Require that participants who previously participated in the research study be informed of the Noncompliance or of other relevant information;
- Modify the study’s continuing review schedule;
- Suspend, in whole or in part, the research protocol;
- Terminate the research protocol;
- Require periodic audits of the study, either announced or unannounced; and/or
- Any other action the IRB deems appropriate in relation to the Serious Noncompliance.
18.104.22.168 Actions with Respect to the Research Personnel Involved in the Serious Noncompliance
The IRB may take one or more of the following actions with respect to the Research Personnel involved in the Serious Noncompliance:
- Require remedial education;
- Require oversight by a senior PI;
- Restrict the conduct of human subjects research activities;
- Restrict or suspend human subject research privileges; and/or
- Make recommendations to the IO regarding other disciplinary actions.
22.214.171.124 Reporting to the IO and Regulatory Agencies
If the IRB determines that the Allegation constitutes Serious Noncompliance or Continuing Noncompliance, further reporting to the IO and/or department or agency head is required in accordance with section 3.7, below.
126.96.36.199 Communication to Research Personnel Involved in the Serious Noncompliance and to the Complainant
The outcome of the IRB review will be communicated in writing to the complainant. The IRB Chair will notify the Research Personnel involved in the Serious Noncompliance, and will send a copy of the findings to the Chair of the Research Personnel’s research unit. Such notice to the Research Personnel will inform them that they have 10 business days from receipt of the notice to request reconsideration. To request reconsideration, the Research Personnel must send the IRB a written request for reconsideration, including the basis and compelling justification for the request. Once submitted, the request will be considered by the IRB Chair or by the IRB at the next Convened IRB meeting, at the discretion of the IRB Chair. A determination will be made whether to uphold, reverse or modify the decision. This determination is final and cannot be appealed or reconsidered. The IRB Chair will notify the Research Personnel of the final outcome.
3.7 Reporting to the IO and Regulatory Agencies
3.7.1 Reporting to the IO
The IRB Chair will report in writing the following events to the IO:
- Noncompliance determined to constitute Serious or Continuing Noncompliance;
- Suspensions; and
The contents of the report for the IO must include the following:
- The title and protocol number of the research study;
- The name of the PI;
- A detailed description of the event;
- The related findings;
- Actions taken to address the issue;
- The basis for the reviewing individual/reviewing committee actions;
- The research study’s IND number (if applicable); and
- Any further investigation or action recommended to be taken (if applicable).
3.7.2 IO Reporting Responsibilities
Within 15 calendar days after receiving the report, the IO (or this individual’s designee) will submit a formal report regarding the matter to the following recipients:
- Office for Human Research Protections (OHRP), if the research study is subject to U.S. Department of Health and Human Services (DHHS) regulations;
- Other federal agencies, if the research study is subject to those agencies and the agency requires reporting separate from that to OHRP;
- FDA, if the research study is FDA-regulated;
- The Sponsor of the research study, if appropriate; and
- The funding source of the research study, if appropriate.
The IO may, at this individual’s professional discretion, make additional reports verbally or in writing to internal offices, committees, or individuals at Brown.
For the purpose of this policy, the terms below have the following 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.
A report that noncompliance may have occurred, and requires further investigation to determine if noncompliance has, in fact, occurred.
Refers to how a researcher has agreed to handle, manage, and disseminate the information disclosed by or data regarding a participant. There is a relationship of trust between these parties and the expectation that confidential information or data will not be divulged to others by the researcher without the participant’s permission in ways that are inconsistent with the agreement regarding the disclosure of the information or data.
- Continuing Noncompliance:
A pattern of noncompliance that indicates a lack of understanding or disregard for the regulations or institutional requirements that protect the rights and welfare of participants and others, compromises the scientific integrity of a study such that important conclusions can no longer be reached, suggests a likelihood that noncompliance will continue without intervention, or involves frequent instances of minor noncompliance. Continuing Noncompliance may also include failure to respond to a request from the IRB to resolve an episode of noncompliance or a pattern of minor noncompliance.
- Convened IRB:
A meeting of the IRB at which a majority of IRB members are present.
- Department of Health and Human Services (DHHS):
The federal agency charged with enhancing and protecting the health and well-being of all Americans by providing for effective health and human services and fostering advances in medicine, public health, and social services.
- Food and Drug Administration (FDA):
The federal agency responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, the U.S. food supply, cosmetics, and products that emit radiation. The FDA is also responsible for regulating the manufacturing, marketing, and distribution of tobacco products, and for advancing the public health by helping to speed innovations that make medical products and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medical products and foods to improve their health.
- Institutional Official (IO):
The individual identified on Brown University’s Federalwide Assurance with the Office for Human Research Protections who is legally authorized to act for and on behalf of Brown University, and who obligates the University to the Terms of the Assurance. At Brown University, the IO is the Vice President for Research.
- Investigational Device Exemption (IDE):
A request for authorization from the FDA to use an investigational device in a clinical research study in order to collect safety and effectiveness data. An approved IDE permits a device to be shipped lawfully for the purpose of conducting investigations of the device without complying with other requirements of the Food, Drug, and Cosmetic Act (FD&C Act) that would apply to devices in commercial distribution.
- Investigational New Drug Application (IND):
A request for authorization from the FDA to administer an investigational drug or biological product to humans. Such authorizations must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved New Drug Application or Biologics/Product License Application.
- Minor Protocol Deviations:
Protocol deviations from IRB-approved procedures that (i) do not cause harm and have no potential to cause harm to research participants or others, and (ii) do not impact the integrity of research data.
Includes (i) a failure to comply with federal, state, or local regulation that governs human subjects research; (ii) a violation of any Brown University policy on human subjects research; and (iii) any unapproved deviation from an IRB/HRPP-approved protocol or stipulations imposed by the IRB/HRPP as a condition of approval, 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. This term is construed broadly.
- Office for Human Research Protections (OHRP):
The federal office providing leadership in the protection of the rights, welfare, and wellbeing of participants involved in research conducted or supported by the U.S. Department of Health and Human Services by offering clarification and guidance, developing education programs and materials, maintaining regulatory oversight, and giving advice on ethical and regulatory issues in biomedical and social/behavioral research.
- Principal Investigator:
An individual with the appropriate scientific and/or scholarly training and expertise to assume direct responsibility for the ethical conduct of a study involving human subjects, providing technical and administrative oversight of the research and making important study-related decisions. For purposes of HRPP policy, only one individual is designated as the principal investigator of a human research study.
Refers to a participant’s right to control who has access to them, their location, and their space. It is the recognition that a participant has the right to determine the extent, timing, and circumstances of sharing themselves (physically, behaviorally, or intellectually) with researchers.
- Reportable Event:
A type of unanticipated event or occurrence related to a human subjects research study that requires review by the IRB as defined in the IRB Reportable Events Policy.
- Research Personnel:
Persons, including the Principal Investigator, who have direct contact with participants, contribute to the research in a substantive way, have contact with a participant's identifiable data or biological samples (e.g., tissue, blood, urine, plasma, saliva), or use a participant's personal information for research purposes.
- Serious Noncompliance:
Noncompliance that (i) significantly increases risks, or significantly decreases potential benefits, to participants; (ii) adversely affects the rights, welfare, and safety of participants; (iii) adversely affects the scientific integrity of a study; (iv) is the result of a willful violation of any federal, state, or local regulation that governs human research; or (v) is a willful violation of any Brown University policy on human subjects research.
An action taken by the convened IRB or the IRB Chair 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 determines to (i) lift the suspension or (ii) terminate the study or some activities of the study.
An action taken by the convened IRB or the IRB Chair to permanently stop all research activities in an approved research study.
- Unanticipated Problems Involving Risk to Subjects or Others (UP):
Any incident, experience, or outcome in the course of human subjects research that is (i) unexpected (in terms of nature, severity, or frequency); (ii) related or possibly related to participation in research; and (iii) 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 Adverse Event (UAE):
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.
All individuals to whom this policy applies are responsible for becoming familiar with and following this policy. University supervisors are responsible for promoting the understanding of this policy and for taking appropriate steps to help ensure compliance with it.
6.0 Consequences for Violating this Policy
Failure to comply with this and related policies is subject to disciplinary action, up to and including suspension without pay, or termination of employment or association with the University, in accordance with applicable (e.g., staff, faculty, student) disciplinary procedures.
7.0 Related Information
Brown University is a community in which employees are encouraged to share workplace concerns with University leadership. Additionally, Brown’s Anonymous Reporting Hotline allows anonymous and confidential reporting on matters of concern online or by phone (877-318-9184).
The following information complements and supplements this document. The information is intended to help explain this policy and is not an all-inclusive list of policies, procedures, laws and requirements.
7.1 Related Policies:
7.2 Related Procedures:
7.3 Related Forms:
7.4 Frequently Asked Questions (FAQs):