Human Research Protection Program (HRPP) — Comprehensive Researcher Site Visit Manual

What am I being asked to do?

This guidance document is a comprehensive evaluation and interview preparation guide designed specifically for Principal Investigators (PIs), Co-Investigators, Clinical Research Coordinators, and Key Research Personnel at Brown University ahead of our Association for Accreditation of Human Research Protections Programs (AAHRPP) site visit. During the site visit, AAHRPP site visitors select active researchers across campus for individual interviews to assess your practical understanding of researcher responsibilities, human participant protections, consent procedures, data security, and institutional workflows.

This manual covers every operational protocol, ethical obligation, Huron Toolkit requirement, and institutional procedure you may be asked about during your site visit interview. 

What is AAHRPP accreditation and why does it matter to researchers?

AAHRPP accreditation uses a voluntary, peer-driven, educational model to evaluate an organization's Human Research Protection Program (HRPP) against rigorous national and international standards. For PIs and research staff, AAHRPP accreditation validates that Brown provides robust support infrastructure, protects research participants to the highest ethical standard, facilitates single IRB (sIRB) reliance agreements with external partners, and enhances competitiveness for federal grants and clinical trial sponsorships.

What rules, guidelines, and ethical principles must PIs follow?

As a researcher conducting human subjects studies at Brown University, your protocols and team practices must align with core ethical standards, federal regulations, state laws, and institutional SOPs:

• The Belmont Report: The cornerstone ethical framework for human research. All Brown researchers must apply its three core principles: 1) Respect for Persons (respecting autonomy, obtaining voluntary informed consent, protecting vulnerable populations), 2) Beneficence (maximizing prospective benefits and minimizing potential risks), and 3) Justice (equitable selection of subjects without bias or unfair burden).
• Revised Common Rule (45 CFR 46): Governs federally funded and university-regulated human subjects research. Protocols approved on or after January 21, 2019, adhere to Revised Common Rule provisions, including concise 'Key Information' consent summaries, revised exempt categories, and eliminated annual continuing review for most minimal-risk protocols.
• Pre-2018 Common Rule: Governs protocols initially approved before January 21, 2019, requiring annual continuing review unless explicitly transitioned by the IRB.
• FDA Regulations (21 CFR 50, 56, 312, 812): Applies to research involving investigational drugs, biologics, medical devices, or FDA-regulated test articles, enforcing strict investigational drug/device management, consent rules, and IRB reporting.
• Good Clinical Practice (GCP): ICH GCP E6 guidelines apply to clinical trials, establishing standards for protocol design, conduct, monitoring, auditing, data collection, and documentation.
• Brown HRPP Policies & Huron Toolkit: Researchers must follow Brown’s HRPP Standard Operating Procedures (SOPs) and utilize Huron investigator guidance documents, templates, and checklists available on the Brown HRPP website.

What is the scope of Brown's HRPP and how do PIs interact with affiliated hospital systems?

Brown’s HRPP oversees all human research conducted by Brown faculty, staff, trainees, and students across all campus departments, academic centers, and schools. Because Brown researchers frequently collaborate with regional health systems, the HRPP maintains integrated oversight and reliance pathways:

• Hospital Affiliations & IRB Reliance: Brown's HRPP oversees human subjects research conducted by Brown faculty, staff, and students across all campus departments, schools, and centers including Brown University Health, and Care New England.
• Single IRB (sIRB) Requirements: For NIH-funded multi-site research or federally funded collaborative studies, PIs must utilize a Single IRB of Record (sIRB). Brown HRPP processes SMART IRB agreements and ceding requests to ensure local context requirements are addressed.
• Inter-Committee Clearances: IRB approval alone does not constitute full institutional authorization. PIs are responsible for securing all requisite ancillary committee approvals prior to initiating research: Biosafety (IBC), Environmental Health & Safety (EHS), Radiation Safety, Conflict of Interest (COI) in Research, Information Technology (OIT Data Security), Export Control, and Sponsored Projects (OSP).

What defines 'Human Subjects Research' and who makes this determination?

Before initiating any study involving people or data, researchers must evaluate whether the activity constitutes Human Subjects Research under federal definitions:

• Research (45 CFR 46.102(l)): A systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.
• Human Subject (45 CFR 46.102(e)): A living individual about whom an investigator conducting research: (1) Obtains data through intervention or interaction with the individual, or (2) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.

What are the review categories and how is risk evaluated?

Human subjects research protocols are processed under three regulatory review categories based on procedure risk and statutory criteria:

• Exempt Review (45 CFR 46.104): Minimal-risk research fitting specific statutory categories (e.g., educational testing, anonymous surveys, benign behavioral interventions, secondary analysis of public/de-identified data). Evaluated administratively by HRPP staff.
• Expedited Review (45 CFR 46.110): Research involving no more than minimal risk that fits into federal expedited categories (e.g., blood sampling from healthy adults, noninvasive biological specimens, survey/interview protocols collecting identifiable data). Reviewed by a single Designated IRB Reviewer.
• Full Board / Convened Review: Research involving greater than minimal risk (e.g., invasive clinical interventions, high-risk drug/device trials, sensitive research with vulnerable populations, or studies presenting significant physical, psychological, or privacy risks). Must be reviewed and approved by the convened IRB.

What is 'Minimal Risk' and what kinds of risk must PIs assess?

According to 45 CFR 46.102(j), minimal risk means that the probability and magnitude 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.

In protocol applications, PIs must thoroughly identify and present risk mitigation strategies for all potential harm categories:

• Physical Risks: Pain, bruising, infection, fatigue, adverse reactions to test articles, or bodily injury.
• Psychological Risks: Emotional distress, trauma trigger, anxiety, guilt, or embarrassment.
• Social & Economic Risks: Loss of employment, insurance discrimination, social stigmatization, or financial loss.
• Legal Risks: Risk of criminal prosecution or civil liability resulting from data breaches exposing illegal activities (e.g., substance abuse, undocumented status).
• Privacy & Confidentiality Risks: Unauthorized disclosure of identifiable personal data or PHI.

What are the core criteria for IRB approval under 45 CFR 46.111?

Site visitors frequently test PIs on the criteria the IRB uses to evaluate protocols. PIs must ensure protocol applications demonstrate compliance with Huron Worksheet HRP-314 criteria:

• 1. Risk Minimization: Risks to subjects are minimized by using procedures consistent with sound research design and avoiding unnecessary risk exposure.
• 2. Risk/Benefit Ratio: Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.
• 3. Equitable Subject Selection: Selection of subjects is equitable, taking into account the purposes of the research, setting, and population (avoiding improper inclusion/exclusion).
• 4. Informed Consent Seeking: Informed consent will be sought from each prospective subject or legally authorized representative (LAR) in accordance with regulatory requirements.
• 5. Consent Documentation: Informed consent will be appropriately documented or validly waived under regulatory criteria.
• 6. Data Safety Monitoring: When appropriate, the research plan makes adequate provision for monitoring collected data to ensure subject safety (e.g., DSMB plans).
• 7. Privacy & Confidentiality: Adequate provisions exist to protect participant privacy and maintain data confidentiality.
• 8. Vulnerable Populations: Additional safeguards are included to protect rights and welfare of vulnerable subjects (e.g., children, prisoners, pregnant women, decisionally impaired).

What are the PI's direct responsibilities in the Informed Consent process?

Informed consent is an ongoing educational process, not just a document signing. PIs are responsible for ensuring that:

• Voluntary Participation: Consent is sought under conditions that provide the prospective subject sufficient opportunity to discuss and consider participation, minimizing coercion or undue influence.
• Understandable Language: Consent documents and verbal disclosures use lay language appropriate for the study population (typically 8th-grade reading level, translated for non-English speakers).
• Key Information Summary: For Revised Common Rule studies, consent forms begin with a concise 'Key Information' summary detailing the purpose, voluntary nature, duration, main procedures, major risks, and prospective benefits.
• Delegation of Consent Authority: Only research team members explicitly trained and authorized in the IRB-approved protocol may conduct the consent conversation.
• Document Management: Participants are provided a copy of their signed consent form. Signed consent documents must be retained securely for the required institutional and regulatory retention period.

When can Informed Consent or Documentation be waived?

PIs cannot decide on their own to omit consent. The IRB may grant waivers under specific statutory criteria using Huron Checklists:

• Waiver/Alteration of Consent (HRP-410): Granted if: 1) Research involves no more than minimal risk, 2) Waiver will not adversely affect subject rights/welfare, 3) Research could not practicably be carried out without the waiver, and 4) Whenever appropriate, subjects are provided additional pertinent information after participation.
• Waiver of Written Documentation of Consent (HRP-411): Granted if: 1) The consent document is the only record linking the subject and the research, and principal risk is breach of confidentiality, OR 2) Research presents minimal risk and involves no procedures for which written consent is normally required outside of research (e.g., online survey).

How must research data and participant privacy be protected?

PIs must establish robust data security controls aligned with Brown Office of Information Technology (OIT) policies and IRB guidelines:

• Data Storage & Encryption: Identifiable electronic research data must be stored on secure, encrypted Brown-approved storage platforms (e.g., Stronghold secure environment for sensitive/restricted data). Storing identifiable participant data on unencrypted laptops, personal devices, or commercial cloud drives is strictly prohibited.
• De-identification & Key Files: De-identify dataset entries using subject ID codes. Keep code-key files physically and electronically separated from master research data in password-protected, encrypted files.
• Certificates of Confidentiality (CoC): NIH-funded research automatically receives a federal CoC protecting identifiable sensitive research data from forced legal disclosure. PIs must adhere to CoC disclosure restrictions.
• HIPAA Compliance: Research involving Protected Health Information (PHI) from covered entities (e.g., hospital partners) requires explicit HIPAA Authorization or an IRB-approved HIPAA Waiver of Authorization (HRP-441).

How are Reportable New Information (RNI), Adverse Events, and UAPs handled by PIs?

PIs are legally obligated to report unexpected occurrences, deviations, and potential risks promptly via the HRPP submission portal using Huron RNI procedures:

• Adverse Event (AE): Any untoward medical occurrence in a participant, regardless of causality.
• Unanticipated Problem (UAP): Any incident or outcome meeting ALL 3 CRITERIA: 1) Unexpected in nature, severity, or frequency, 2) Related or possibly related to research participation, and 3) Suggests that the research places participants or others at a greater risk of harm than previously recognized.
• Reporting Timelines: PIs must report potential UAPs, serious adverse events (SAEs), protocol deviations that impact participant safety, or safety notifications to the Brown HRPP promptly within the required institutional timeframe (typically within 5 business days of becoming aware).

What constitutes Noncompliance and how must PIs address it?

• Noncompliance Definition: Failure by research personnel to follow federal regulations, state laws, IRB determinations, or institutional HRPP policies.
• Serious Noncompliance: Noncompliance that adversely affects subject rights, safety, or welfare, increases risk, or compromises research data integrity.
• Continuing Noncompliance: A recurring pattern of noncompliance indicating persistent lack of knowledge or unwillingness to comply with regulatory requirements.
• PI Responsibility: PIs must report any protocol noncompliance or deviations immediately. PIs must cooperate with HRPP fact-finding inquiries, implement IRB-mandated Corrective and Preventive Action (CAPA) plans, and complete all required remediation steps.

What are the rules regarding Protocol Modifications / Amendments?

No changes, revisions, or amendments to an IRB-approved protocol, consent form, study instrument, recruitment material, or research personnel may be implemented prior to formal IRB review and approval.

What are the PI's obligations regarding Conflict of Interest (COI)?

PIs and all key research personnel must disclose all financial interests, external consulting, equity, or commercial relationships related to proposed research:

• Disclosure Process: Financial interests are disclosed in the IRB application and submitted to the Brown Conflict of Interest in Research Committee.
• COI Management Plans: If a financial conflict exists, the COI Committee establishes a formal Management Plan. PIs must comply with all management provisions (e.g., independent consent monitors, disclaiming financial interest in consent forms). The IRB maintains final authority to evaluate whether the management plan adequately protects human subjects.

How do PIs handle FDA-regulated drugs, biologics, and medical devices?

If research involves investigational drugs, biologics, or medical devices, PIs must fulfill specialized regulatory duties:

• Investigational New Drug (IND) Applications: Research evaluating an unapproved drug or an approved drug for a new indication/population requires an IND number from the FDA unless determined IND-exempt under 21 CFR 312.2 (evaluated using Huron Worksheet HRP-306). PIs must securely store and account for test articles.
• Investigational Device Exemptions (IDE): Device studies require IDE status under 21 CFR 812. Significant Risk (SR) device protocols require FDA IDE approval prior to IRB submission. Non-Significant Risk (NSR) device protocols require an initial SR/NSR rationale from the PI/sponsor, evaluated by the IRB using Huron Checklist HRP-418.
• Investigational Product Accountability: PIs must maintain meticulous accountability logs tracking receipt, dispensing, administration, storage conditions, and destruction/return of all investigational products.

What training and oversight responsibilities do PIs have for research staff?

The PI maintains ultimate responsibility for the conduct of the research study. PIs must ensure that:

• Mandatory CITI Training: All research personnel complete required CITI Human Subjects Protection and GCP training before interacting with subjects or handling identifiable data.
• Delegation of Authority Log: The PI maintains clear delegation of research duties, ensuring personnel are qualified, trained, and authorized for their specific tasks.
• Ongoing Oversight: The PI provides continuous oversight, regular team communication, and supervision across all study sites and research activities.

What should PIs expect during an AAHRPP site visit interview?

During your site visit interview, AAHRPP visitors will ask open-ended questions to evaluate your practical application of human research protections. Be prepared to answer questions such as:

• 1. How do you ensure potential participants understand the research before signing consent?
• 2. What steps do you take if a participant experiences an unexpected adverse reaction?
• 3. How do you protect participant privacy and secure electronic data on your team?
• 4. What is the process for submitting protocol changes before implementing them?
• 5. How do you determine whether a research staff member is qualified to obtain consent?
• 6. Who do you contact if you have questions regarding IRB policies or regulatory compliance?

Remember: Answer candidly, describe your actual daily research practices, and emphasize your commitment to participant safety and institutional compliance. 

Human Research Protection Program (HRPP) — Comprehensive Site Visit Manual

What am I being asked to do?

This guidance document is a comprehensive evaluation and interview preparation guide designed specifically for Brown University Institutional Review Board (IRB) members ahead of our Association for Accreditation of Human Research Protections Programs (AAHRPP) site visit. During the site visit, AAHRPP site visitors conduct individual, structured interviews with IRB members to evaluate your understanding of federal regulations, Brown HRPP Standard Operating Procedures (SOPs), ethical principles, and operational workflows.

This document walks through every core concept, regulatory standard, Huron Toolkit checklist, and operational procedure you may be asked about during your interview. If you would like additional assistance or a mock interview session before your site visit, please contact Ally Boutros, Director of the Human Research Protection Program (ally_boutros@brown.edu).

What is AAHRPP accreditation?

AAHRPP accreditation uses a voluntary, peer-driven, educational model to ensure that a Human Research Protection Program (HRPP) meets rigorous international standards for quality, ethical integrity, and subject protection. The primary goals of accreditation are to improve the systems that protect the rights and welfare of human research participants and to demonstrate to the public, sponsors, and peer institutions the strength of Brown University's institutional commitment to human research protections.

What rules or guidelines do you follow?

As an IRB member at Brown University, your reviews must evaluate protocols against several key ethical frameworks, federal regulations, state laws, and institutional SOPs:

• The Belmont Report: The foundational ethical framework applied to all human research at Brown, regardless of funding source. It establishes three core principles: 1) Respect for Persons (autonomy and protection of vulnerable individuals), 2) Beneficence (maximizing benefits while minimizing harms), and 3) Justice (equitable selection of subjects and distribution of research burdens/benefits).
• Revised Common Rule (45 CFR 46): The federal regulatory framework governing human subjects research. Protocols approved on or after January 21, 2019, are subject to the Revised Common Rule, which streamlined minimal-risk oversight (eliminating annual continuing review for most minimal-risk non-exempt studies) and added mandatory 'Key Information' summary requirements to consent documents.
• Pre-2018 Common Rule: Protocols approved prior to January 21, 2019, remain governed by the pre-2018 Common Rule unless formally transitioned by the IRB.
• FDA Regulations (21 CFR 50, 56, 312, 812): Governs clinical investigations involving FDA-regulated drugs, biologics, or medical devices, enforcing specific consent and IRB operational requirements.
• OHRP & Federal Agencies: The Office for Human Research Protections (OHRP) oversees HHS-funded research. Brown also complies with agency-specific rules (e.g., Department of Defense, Department of Energy, Department of Justice) when applicable.
• Brown HRPP Policies & Huron Toolkit: Brown has adopted the standardized Huron HRPP Toolkit, which structures our Standard Operating Procedures (SOPs), checklists, and evaluation worksheets. All policies are accessible via the Brown HRPP website.

How does the HRPP and IRB interact with Campus and Affiliated Hospital Systems?

Brown’s HRPP operates an integrated oversight model that covers academic departments across campus while coordinating closely with affiliated health systems and external research entities:

• Campus & Hospital Integration: Brown's HRPP oversees human subjects research conducted by Brown faculty, staff, and students across all campus departments, schools, and centers including Brown University Health, and Care New England.
• Single IRB (sIRB) & Ceded Reviews: For multi-center research, Brown uses SMART IRB and reliance agreements to cede review to an external IRB or serve as the Single IRB of Record. HRPP staff process reliance requests and ensure local context requirements are fulfilled.
• Inter-Committee Coordination: The IRB works in close coordination with other institutional oversight committees. An IRB approval is contingent upon necessary clearances from Biosafety (IBC), Environmental Health & Safety (EHS), Radiation Safety, Conflict of Interest (COI) in Research Committee, Information Technology (OIT Data Security), Export Control, and the Office of Sponsored Projects (OSP).

What does the IRB do? Who do IRBs protect? What is your role?

The primary objective of the IRB is to safeguard the rights, safety, and welfare of human research participants. As an IRB member, your specific duties include:

• Convened Meeting Attendance: Attending scheduled full-board meetings and participating in substantive ethical and scientific discussions.
• Pre-Meeting Preparation: Thoroughly reviewing all assigned submission materials on the agenda—including protocol applications, grant proposals, consent documents, recruitment flyers, questionnaires, and investigator brochures—at least one week prior to the meeting.
• Criteria Evaluation: Evaluating proposals using Huron Toolkit worksheets to verify that all statutory criteria for IRB approval under 45 CFR 46.111 / 21 CFR 56.111 are satisfied.
• Designated Reviews: Serving as a Designated Reviewer for expedited initial reviews, amendments, continuing reviews, and administrative reviews when assigned by the IRB Chair or HRPP Director.

What are the requirements for IRB membership?

Federal regulations dictate that IRB membership must possess the professional expertise and diversity necessary to evaluate research protocols thoroughly. An IRB must have at least five members representing three distinct categories:

• Scientific Members: Members with primary expertise in scientific or medical disciplines who evaluate the research design, scientific validity, methodology, and safety standards.
• Non-Scientific Members: Members whose primary training and background are non-scientific (e.g., ethicists, lawyers, clergy, literature scholars). They ensure protocols and consent materials are understandable from a lay perspective and prioritize subject rights.
• Non-Affiliated (Community) Members: Members who have no employment, formal affiliation, or immediate family connections to Brown University. They represent the perspective of the local community and research participants.

What is the authority of the IRB?

The IRB has the explicit authority to approve, require modifications to secure approval, defer, suspend, or terminate research involving human subjects. The IRB also has the authority to observe, or appoint a third party to observe, the informed consent process and the conduct of research.

What is ethical research?

Ethical research is research conducted in strict accordance with the Belmont Report principles and statutory criteria for approval (45 CFR 46.111). Risks to subjects must be minimized through sound research design, risks must be reasonable in relation to anticipated benefits, selection of subjects must be equitable, informed consent must be sought and documented appropriately, and participant privacy and data confidentiality must be protected.

What is the full board / convened meeting process?

All protocol submissions assigned to full-board review are pre-screened by HRPP staff and distributed to IRB members at least one week prior to the scheduled meeting. Submissions include the protocol application, consent forms, recruitment materials, data collection instruments, grant proposals, and Huron review worksheets.

Brown IRB uses a Primary Reviewer model. Assigned reviewers lead the presentation and discussion of the protocol at the convened meeting and complete the required Huron worksheets. All attending members are expected to review the agenda materials, participate in discussion, and vote on motions.

What motions can you make at a convened meeting?

At a convened meeting, the IRB may vote on the following motions for any submission:

• Approved: The protocol meets all approval criteria with no changes required.
• Modifications Required to Secure Approval: The IRB requires specific, non-substantive modifications that can be verified administratively by HRPP staff or the IRB Chair without returning to the full board.
• Deferred / Table: The protocol requires substantive revisions or additional information before the IRB can complete its regulatory evaluation. The resubmission must return to the convened IRB.
• Disapproved: The protocol fails to satisfy statutory approval criteria and cannot proceed.
• Suspended or Terminated: Approval of previously authorized research is suspended or permanently revoked (e.g., due to serious noncompliance or unexpected risk).

Do you have written checklists that you can use during your review?

Yes. Brown University HRPP utilizes the standardized Huron HRPP Toolkit worksheets and checklists, which are available directly on the Brown HRPP website. Members utilize these tools to guide and document regulatory evaluations:

• HRP-314 Worksheet: Criteria for Approval (primary worksheet evaluating risk/benefit, consent, safety monitoring, privacy).
• HRP-405 Checklist: Limited IRB Review (evaluating exempt research categories requiring limited review).
• HRP-410 & HRP-411 Checklists: Waiver or Alteration of Consent Process / Waiver of Written Documentation of Consent.
• Vulnerable Populations Checklists: HRP-412 (Pregnant Women & Fetuses), HRP-415 (Prisoners), HRP-416 (Children), and HRP-417 (Cognitively Impaired Adults).
• Device & Drug Worksheets: HRP-418 (Non-Significant Risk Device Determinations) and HRP-306 (Investigational Drugs & Biologics).
• HRP-441 Checklist: HIPAA Waiver of Authorization.

What is minimal risk and how is it evaluated?

According to 45 CFR 46.102(j), minimal risk means that the probability and magnitude 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.

Risk evaluation encompasses physical, psychological, social, legal, and financial harms. Evaluators assess procedure intensity, participant baseline vulnerability, and safety protections (e.g., data encryption, clinical supervision) to determine if a study is minimal risk or greater than minimal risk.

What are the kinds and levels of risk?

• Physical Risks: Bodily harm, pain, fatigue, side effects from drugs/devices, or physical injury.
• Psychological Risks: Emotional distress, anxiety, embarrassment, trauma, or psychological discomfort.
• Social & Financial Risks: Stigmatization, loss of employment, reputation damage, or financial liability if private data is breached.
• Legal Risks: Criminal or civil liability resulting from disclosure of illegal behavior or sensitive data.
• Minimal Risk vs. Greater than Minimal Risk: Minimal risk studies qualify for administrative exempt or expedited review. Studies involving greater than minimal risk must be reviewed by the convened IRB.

What are exempt and expedited reviews, and when are they used?

• Exempt Review: Research involving minimal risk that falls within specific statutory exemption categories under 45 CFR 46.104 (e.g., educational research, benign behavioral interventions, survey research, public data analysis). Investigators cannot self-determine exemption; exempt determinations must be made administratively by Brown HRPP staff.
• Expedited Review: Research involving no more than minimal risk that fits into one of the federal expedited categories (45 CFR 46.110 / 21 CFR 56.110), such as blood draw protocols, noninvasive specimen collection, or survey/interview research not qualifying for exemption. Expedited reviews are conducted by a single Designated Reviewer appointed by the IRB Chair.

What is the difference between exempt and not human subjects research?

• Exempt Research: Meets both definitions of 'Human Subject' and 'Research', but the procedures present minimal risk and fit statutory exemption categories under 45 CFR 46.104.
• Not Human Subjects Research (NHSR): The activity either does not meet the federal definition of 'Research' (a systematic investigation designed to develop or contribute to generalizable knowledge) OR does not involve 'Human Subjects' (obtaining data/biospecimens through intervention/interaction with a living individual, or obtaining identifiable private information). NHSR activities do not require full IRB review.

Who makes the not human subjects research determination?

At Brown University, formal NHSR determinations are made administratively by experienced Brown HRPP staff or designated IRB reviewers using Huron Worksheet HRP-310 (Human Research Determination). Investigators are not permitted to make independent NHSR determinations.

Who can perform an administrative review of an IRB submission?

Experienced HRPP staff may perform administrative reviews. This includes making exempt and NHSR determinations, verifying study closures, administrative check-ins, and confirming that required minor modifications requested by the convened IRB have been satisfied.

Who do you go to for help on review issues (ethical or regulatory)?

If you have questions regarding ethical principles, regulatory interpretation, or protocol review criteria, you should contact the HRPP Leadership, the HRPP staff assigned to the protocol, or the IRB Chair.

What is an adverse event? What is an unanticipated problem (UAP)?

• Adverse Event (AE): Any untoward or unfavorable medical occurrence, symptom, or disease in a participant associated with research participation, regardless of causal relationship.
• Unanticipated Problem (UAP): Any incident, experience, or outcome that meets ALL THREE of the following criteria: 1) Unexpected (in terms of nature, severity, or frequency), 2) Related or possibly related to participation in the research, and 3) Suggests that the research places participants or others at a greater risk of harm than was previously known or recognized.

How are unanticipated problems reviewed by the HRPP and the IRB?

PIs must report potential UAPs promptly to the HRPP. HRPP staff screen the report (Huron Worksheet HRP-321) and refer it to the IRB Assistant Directors or IRB Chair(s). If the event is determined to be a potential UAP, it is submitted to the convened IRB for full-board review. If the IRB determines a UAP occurred, it evaluates corrective action plans and triggers mandatory federal reporting to OHRP, FDA, funding agencies, and institutional officials.

What is noncompliance? What is considered serious and/or continuing noncompliance?

• Noncompliance: Failure to follow federal regulations, IRB determinations, or institutional HRPP policies and procedures.
• Serious Noncompliance: Noncompliance that adversely affects the rights, safety, or welfare of participants, increases risk of harm, or compromises research data integrity.
• Continuing Noncompliance: A pattern of noncompliance indicating persistent failure or unwillingness to comply with regulations, policies, or IRB requirements.

How is noncompliance reviewed by the HRPP/IRB?

Reports of noncompliance are screened by HRPP leadership. HRPP staff initiate fact-finding activities (under Huron SOP HRP-024 New Information), which may involve protocol audits or investigator interviews. If evidence of serious or continuing noncompliance exists, the matter is referred to the convened IRB.

Who determines when serious or continuing noncompliance has occurred?

Only the convened IRB at a full-board meeting has the authority to make formal determinations of serious or continuing noncompliance. The IRB determines required corrective actions (e.g., protocol suspensions, consent revisions, re-consenting subjects) and mandates federal reporting.

What is a continuing review?

• Continuing Review: Formal IRB review required at least annually for pre-2018 Common Rule studies, FDA-regulated research, or protocols where the IRB explicitly determined continuing review was required. Evaluates study progress, safety data, and enrollment numbers.

What training/education have you had as an IRB member?

Site visitors will ask about your onboarding and continuing education. Members must complete mandatory CITI Human Subjects Research training, attend new member orientation with HRPP leadership, and participate in ongoing educational presentations provided at convened meetings.

How do you learn of new or revised policies or procedures?

Policy updates are communicated via email notifications from the HRPP Director, featured during educational slots at convened board meetings, and published on the Brown HRPP website.

Who is responsible for evaluating the scientific merit of studies?

Scientific merit is initially evaluated by funding agency peer review and departmental committees. However, under 45 CFR 46.111(a)(1), the IRB is legally obligated to evaluate whether research design is scientifically sound to ensure subjects are not exposed to unnecessary risks for scientifically invalid studies.

Who do you go to if you are feeling pressured by undue influence as a reviewer?

IRB members must exercise independent judgment free from undue influence. If you feel pressured by department chairs, investigators, or administrators regarding a review, you should immediately contact HRPP Director Ally Boutros or the Institutional Official.

Who is the Institutional Official (IO)? What do they do?

At Brown University, the Vice President for Research serves as the Institutional Official (IO). The IO holds ultimate administrative authority for the HRPP, signs Federalwide Assurances (FWA), appoints IRB members, and ensures the IRB operates with complete independence and adequate resources.

As an IRB member, what do you have to do with respect to potential conflicts of interest (COI)?

Before reviewing research, IRB members must evaluate whether they have a financial or personal conflict of interest (Huron SOP HRP-050). If a member has a COI on a protocol scheduled for full board, they must disclose the COI, stay only to answer questions, and leave the meeting room for discussion and voting. They do not count toward quorum.

How do you know if the PI or other research personnel have a COI on a study?

Investigators disclose financial interests during submission. Disclosures are evaluated by the Brown Conflict of Interest in Research Committee. If a COI exists, an approved COI Management Plan is provided to the IRB, which retains final authority to decide if the plan adequately protects human subjects.

How is your IRB service evaluated and do you ever receive feedback?

The IRB Chair and HRPP Assistant Directors conduct annual evaluations of IRB member performance (Huron Worksheet HRP-327), reviewing attendance, protocol preparation, and contributions, providing feedback to strengthen committee performance.

Does the IRB ever utilize consultants to assist with reviews?

Yes. Under Huron SOP HRP-051, if the IRB lacks specific expertise required to evaluate a study (e.g., specialized medical procedures or vulnerable community dynamics), the IRB Chair or IRB Staff invite qualified consultants to review study materials and advise the board.

Who determines when an Investigational New Drug (IND) application is needed?

The investigator discloses drug details in the submission. The IRB and HRPP staff utilize Huron Worksheet HRP-306 to evaluate whether an FDA IND application is required or if the study meets FDA IND exemption criteria (21 CFR 312.2).

When is an Investigational Device Exemption (IDE) needed?

Clinical evaluations of medical devices require an IDE unless exempt under 21 CFR 812.2(c). Significant Risk (SR) device studies require an FDA-approved IDE application prior to IRB approval. Non-Significant Risk (NSR) device studies follow abbreviated IDE requirements.

Who makes a significant / non-significant risk determination on research involving an investigational device?

The PI/sponsor provides an initial SR/NSR assessment. The convened IRB makes the final SR/NSR determination using Huron Checklist HRP-418, documenting its rationale in the meeting minutes.

How do you identify additional requirements from federal funding agencies?

HRPP staff pre-review submissions to identify federal funding agencies (e.g., DoD, DoE, DOJ) and attach agency-specific checklist extensions to ensure compliance with specialized federal rules.

Does the HRPP have an emergency preparedness plan?

Yes. Brown HRPP maintains continuity of operations under emergency response plans (Huron SOP HRP-065) to safeguard research participants and ensure uninterrupted IRB oversight during emergencies or campus disruptions.