AAHRPP Site Visit Guide

You have been selected by the Association for Accreditation of Human Research Protections Program (AAHRPP) to be interviewed during UT Austin’s reaccreditation site visit. This guidance is intended to help you prepare for your interview, and contains common information that may be touched on by the interviewers. If you would like additional assistance preparing for your interview, please contact the Office of Research Support and Compliance (RSC) at orsc@uts.cc.utexas.edu.

AAHRPP uses a voluntary, peer-driven and educational model to ensure that a Human Research Protections Program (HRPP) meets rigorous standards for quality and protection. The goals of accreditation are to improve the systems that protect the rights and welfare of individuals who participate in research, and to communicate to the public the strength of an organizations commitment to the protection of human research participants.

The IRB follows several sets of guidelines and regulations including:

Common Rule: The regulations that govern IRB operations and establish the 46.111 criteria for approval of research. UT Austin applies the Common Rule to the approval of all expedited and full board studies.

The Belmont Report: The three ethical principles that UT Austin applies to all research. These principles are: 1) Respect for persons; 2) Beneficence; 3) Justice. For the full report, go to the HHS website: https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html

UT Austin Policies and Procedures: These include UT Austin specific policies as well as federal regulations. For the full manual, go to the RSC website: https://research.utexas.edu/ors/human-subjects/irb-policies-and-guidance/policies-and-procedures/

Office for Human Research Protection: The Office for Human Research Protections (OHRP) oversees operation of the IRB and provides leadership in the protection of the rights, welfare, and wellbeing of subjects involved in research conducted or supported by the U.S. Department of Health and Human Services (HHS). OHRP is the office to which any serious/continuing noncompliance or unanticipated problems are reported.

FDA (Food and Drug Administration): When submissions include FDA regulated drugs, devices or biologics, UT Austin follows the FDA regulations for research, 21 CFR 56.

HIPAA: The "Privacy Rule," also known as the Health Insurance Portability and Accountability Act establishes minimum federal standards for safeguarding the privacy of individuals’ identifiable health information. Researchers using PHI must typically obtain HIPAA authorization from subjects or the IRB approves a waiver of authorization.

The IRB’s primary objective is to protect the rights, safety, and welfare of human subjects in research. UT Austin has two IRBs: a Social, Behavioral, and Educational (SBE) IRB and a Health Science (HSR) IRB. These IRBs review and approve human subjects research in accordance with the applicable guidelines and regulations listed above.

As an IRB member your duties include:

1. Attending the convened IRB meetings.
2. Reviewing the materials for all submissions on each meeting agenda, including initial submissions, amendments, continuing reviews, adverse events, noncompliance reports, and protocol deviations.
3. Reviewing all documents (the research protocol, IRB application, informed consent form, grant application, questionnaires, advertisements, and any other applicable documents for all research proposals) and providing written recommendations and stipulations to ensure that research protocols comply with the regulations.
4. Reviewing expedited initial submissions, amendments, and continuing reviews (when assigned).

Research must meet approval criteria as defined by federal regulations (45 CFR 46.111). This includes minimizing risk to subjects, designing sound research that does not unnecessarily expose subjects to risk. Research should advance scientific understanding and promote human welfare. Subjects should not be asked to participate in a flawed study exposing them to risk or even inconvenience.

All review submissions (including initial review applications, applications for continuation, change in research, reports of unanticipated problems, or applications for study closure) are screened by RSC staff prior to assignment to a panel meeting and reviewers. All submitted study materials are distributed to reviewers and attending IRB members in sufficient time prior to the meeting to allow for adequate review, typically no later than 14 days before the meeting. This includes the preliminary meeting agenda, the previous month’s minutes, any educational items, and all submitted materials including but not limited to the study proposal, consent document(s), recruitment materials, data collection instruments/measures, and investigator’s brochure/drug labeling.

The UT Austin IRB uses a primary/secondary reviewer system, both of whom are responsible for leading the discussion of the study during the meeting and for completing the required checklists.

Barring holidays and other conflicts, meetings are typically held on the 4th Monday of each month for the Social, Behavioral, and Educational (SBE) IRB and on the 4th Wednesday of each month for the Health Science (HSR) IRB.

IRBs have prepared written checklists for protocol review. These checklists are developed by the IRB staff, and based on current regulations (federal, state and institutional). These checklists are available on the UT Austin IRB website in the IRB Member Resources page.

According to the federal regulations [45CFR46.102 (i)], "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 includes not only physical risk, but also psychological, emotional, legal, social, and financial.

The IRB evaluates the study procedures to determine the risk of a study. The IRB also looks at what may be in place for a study that helps to mitigate risk, such as experience of research personnel in conducting procedures, medical care available in the event of a problem, confidentiality procedures, etc.

The definition of minimal risk serves as the starting point for the determination of the category of review. If a project meets the definition of minimal risk, and falls into an exempt or expedited category, the Chair, Vice Chair, or designated IRB member may review and approve the project. Studies that are greater than minimal risk must be reviewed by the full board.

A risk is a potential harm or injury associated with the research that a reasonable person in the subject's position would likely consider injurious. Risks can be categorized as physical, psychological, sociological, economic, and legal. Risks to subjects must be reasonable in relation to anticipated benefits, if any, to subjects; and to the importance of knowledge that may reasonably be expected to result from the research.

Minimal Risk: the risks of harm anticipated in the proposed research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. These are risks that reflect background risks that are familiar and part of the routine experience of life for an average person in the general population.

Greater than Minimal Risk: The probability and magnitude of harm or discomfort anticipated in the research are greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. Research that is greater than minimal risk is reviewed at full board meetings.

If the study is minimal risk, the designated reviewer considers whether the research falls into an exempt or an expedited review categories. Only the IRB may determine which activities qualify for an exempt review. Investigators do not have the authority to make an independent determination that research involving human subjects is exempt.

Expedited Review

Research that falls within the scope of one of the expedited categories of research defined by federal regulation may be reviewed via expedited review, meaning by a single IRB member (45 CFR 46.110, 21 CFR 56.110 and 38 CFR 16.110). Expedited review categories applies to research that involves no more than minimal risk.

https://www.hhs.gov/ohrp/regulations-and-policy/guidance/categories-of-research-expedited-review-procedure-1998/index.html

Exempt Review

Research may be granted exempt status by the IRB if all research activities involve procedures listed in one or more of the specific categories under 45 CFR 46.101(b).

• https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html#46.101
• https://research.utexas.edu/ors/human-subjects/irb-policies-and-guidance/policies-and-procedures/#5-4-exempt-research

Certain activities have characteristics of research but do not meet the regulatory definition of human subjects research. Some studies fall in gray areas and it is difficult to determine if in fact they are human subjects research and require IRB review. To be considered research, a study must involve human subjects and be research. Below are the federal definitions of each.

Does a study involve Human Subjects?

To involve human subjects, a study must involve a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual OR the study must involve a living individual about whom an investigator conducting research obtains identifiable private information.

Is the activity Research?

To be considered research, the activity must be a systematic investigation including research, development, testing and evaluation, AND the activity must be designed to develop or contribute to generalizable knowledge. If a study does not meet both definitions, it is not human subjects research (NHSR) and does not require IRB review.

Determinations of whether or not activities constitute human subjects research are made by RSC staff who will also determine of the proposed research must be reviewed by the IRB.

You may contact any of the following to help answer your questions: IRB Chair, Vice Chair, other IRB members, and RSC staff.

Unanticipated Problem (UAP): An unanticipated problem involving risk to participants or others is defined by meeting ALL 3 of the following criteria:

1. Unexpected (in terms of nature, severity, or frequency) given the research procedures that are described in the protocol-related documents and the characteristics of the subject population being studied;
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.

UAPs are "unanticipated" and therefore are generally not previously identified in the consent document. Anticipated problems occurring at a greater severity or frequency than previously expected may qualify as unanticipated problems reportable to the IRB.

Adverse Events (AE): a subset of unanticipated problems involving risks to the subject or others and are related to untoward or unfavorable medically-related events, including any abnormal sign, symptom or disease temporarily associated with the subject’s participation in the research or clinical trial.

The IRB requires principal investigators to promptly report a summary of each UAP involving risks to subjects and others to the IRB. Upon receipt, RSC staff will screen the report. The report, with the RSC staff’s recommendation, is then reviewed by the IRB Chair, Vice Chair, or RSC Director who will determine whether the report likely represents an unanticipated problem.

If the reported problem clearly does not meet the unanticipated problem criteria the report will be acknowledged. All reports will also be reviewed to determine if there are issues of possible noncompliance.If initial review indicates that the report is likely an unanticipated problem involving risks to subjects or others, study documents such as the protocol and consent form will be provided to the IRB members for review prior to the convened meeting.

The IRB will consider whether the event meets all three criteria for an unanticipated problem involving risks to subjects or others. If after reviewing the information, the IRB determines that the event was not an unanticipated problem, the issue will be returned to the RSC to be handled administratively.

Noncompliance means that researchers or individuals other than researchers, such as research staff, Institutional Review Board (IRB) staff, or IRB members, did not adhere to Federal Regulations and/or The University of Texas at Austin policies, procedures, requirements, or IRB determinations for conducting research involving human subjects.

Serious noncompliance is noncompliance that materially increases risks, that results in substantial harm to subjects or others, or that materially compromises the rights or welfare of research participants.

Continuing noncompliance is a pattern of repeated noncompliance that if continued will likely, in the IRB’s judgment, materially adversely affect the rights, welfare or safety of research participants, the integrity or validity of the related research, or the work of the IRB.

Findings of serious and/or continuing noncompliance must be reported to regulatory authorities and the sponsor.

Upon receipt of a report or allegation of noncompliance or upon identifying noncompliance as part of the review process, RSC staff will make an initial assessment to determine whether the problem may rise to the level of serious and/or continuing noncompliance.

The RSC initiates fact-finding activities, which may include reviewing study documentation and corresponding with the principal investigator and research personnel to determine whether the allegation is substantiated. The IRB Chair/ IRB reviewer(s) may participate with the RSC as needed. In the event that the investigation finds evidence that serious and/or continuing noncompliance may have occurred, the problem will be referred to the convened IRB.

The full board determines when serious or continuing noncompliance has occurred at a convened meeting. The IRB will also determine what restrictions, conditions, or other remedial actions are necessary to resolve the noncompliance and the procedures required to prevent future occurrences. The researcher is notified in writing of the IRB’s determination and of any required corrective actions. Regulatory agencies will also be notified as applicable.

Any research activity involving the use of human subjects that has received initial review and approval by an Institutional Review Board (IRB) is subject to continuing review and approval. Time intervals for such reviews shall be made at the discretion of the IRB based on the anticipated risks to subjects but shall occur no less than once per year. IRB reviewers have access to the continuing review application, current IRB approved study documents, all previously approved amendments, reportable events, previous continuing reviews, and correspondence between the IRB and research team during their review of the continuing review application.

Generally, if a protocol was approved at a convened meeting of the IRB at initial review it must be reviewed at a convened meeting of the IRB for its continuing review. However, if the research initially did not qualify for expedited review the IRB may designate the protocol as minimal risk and determine that the protocol may undergo an expedited review process under Category 9. This determination can be made at the time of initial review or at a subsequent continuing review.

No research protocol may continue after approval has expired until final approval for continuation is granted.

The answer will be member-specific, but all IRB members are required to maintain up to date CITI certification and attend new member orientation and meetings as guests prior to joining the IRB. Additionally, RSC staff provide educational presentations and materials at the beginning of meetings. Members may also attend conferences or other presentations relevant to IRB membership (i.e. webinars provided by RSC).

Members are informed by the Chair or RSC staff of new or revised policies or procedures at the beginning of full board meetings. New policies or procedures are also sent out via email and/or updated on the RSC website.

Scientific merit is evaluated by funding agencies, at the departmental level by departmental reviewers, and by the IRB. The Criteria for IRB Approval (46.111) specify that risks to subjects must be minimized by using sound research design, and that risks to subjects are reasonable in relation to anticipated benefits and the importance of the knowledge to be gained.

Typically the first step would be to speak with your IRB chair. If you feel the undue influence is from the chair, you can also speak to the Institutional Official (IO), the Director of RSC, or another staff member of RSC.

At The University of Texas at Austin the Vice President for Research, Dr. Dan Jaffe, is the IO. The IO is responsible for ensuring that the human research protection program has the resources and support necessary to comply with all federal regulations and guidelines that govern human subjects research. The IO is legally authorized to represent the institution, is the signatory official for all Assurances, and assumes the obligations of the institution's Assurance.

Prior to discussion of protocols at a convened meeting, the IRB Chair will ask if any member has a COI with any protocol being discussed at that meeting. A conflict of interest may include financial interests of the IRB member or immediate family members (spouse, domestic partner, and dependents) as well as nonfinancial issues. A financial interest exists when the member has financial relationship with the sponsor, product or service being tested. Examples of nonfinancial conflicts held by members include philosophic or moral objection to the study itself, supervisory or subordinate positions relative to the principal investigator, participation in a promotion or tenure evaluation relative to a protocol investigator, or service on a graduate student investigator’s committee for the research.

Should an IRB member declare involvement in any way in a research protocol under review by the IRB, or state a COI with the research protocol the following is required:

1. IRB member is excluded from discussion and voting except to provide information requested by the IRB.
2. IRB member leaves the meeting room during discussion and voting.
3. IRB member is not counted towards quorum.

IRB members with a conflict are documented in the minutes as being absent with an indication that a conflict of interest was the reason for the absence.

The PI is responsible for identifying all investigators and personnel associated with the research. These individuals are required to complete a Financial Interest Disclosure (FID). For each IRB submission, the COI committee conducts a review of each COI Investigator and determines whether a financial Conflict of Interest exists. If a conflict of interest is found, the COI committee develops a plan for managing, reducing, or eliminating the conflict that must be adopted. The management plan is provided to the assigned IRB reviewers and the Chair. The IRB can impose additional requirements on top of the COI committee requirements.

IRB members complete a member survey annually, which serves as a self-evaluation. These results are used by RSC staff and Chairs to identify areas of needed education and process improvements and shared with members at a convened meeting. IRB chairs and RSC staff also provide feedback to members throughout the year, either generally or in response to specific reviews.

This is study-specific, so depending on the panel to which you belong, you may or may not have seen a consultant used.  If the IRB does not have a member with the appropriate expertise to review a protocol, a consultant can be brought in to advise the IRB on a particular study.

The IRB is responsible for determining whether an IND is required for studies using an investigational drug, and verification of the IND prior to IRB approval is the responsibility of the primary reviewer.  If the IRB determines that the study does not require an IND and approves the study, the study may begin without submission of an IND application to FDA. If the IRB determines that an IND is needed, the investigator/sponsor must submit an IND application to the FDA and provide documentation of the outcome of the FDA determination to the IRB before the IRB approves the study. Acceptable documentation to verify an IND includes a sponsor protocol with the IND number on it, documentation from the FDA indicating an IND has been approved, or documentation of an IND application having been submitted to the FDA more than 30 days prior (once 30 days have passed without FDA response, an IND is considered approved).

The sponsor or investigator makes the initial significant/non-significant risk (SR/NSR) device determination for research involving an investigational device. The IRB then makes its own assessment, and the device determination is documented in the minutes with the rationale used by the IRB. If the IRB determines that the study using the device is not “significant risk,” it will document that determination in the primary and secondary reviewer checklist and the minutes, along with the IRB’s rationale for that decision. The IRB will notify the PI of its determination and the study may begin without submission of an IDE application to the FDA.

If the IRB disagrees with the sponsor’s or PI’s assessment that a device study is “non-significant risk” and determines that the study using the device is “significant risk,” it will notify the PI, and where applicable, the sponsor (21 CFR 812.66) and document its determination in the IRB minutes. The study will be tabled, the sponsor or PI must apply for an IDE, and the study may not begin until the FDA approves the IDE application and the IRB approves the study. Upon receipt of FDA approval, the sponsor or PI must provide the IRB with the FDA’s approval letter or conditional approval letter as part of the re-submission process.

FDA has the ultimate decision in determining if a device study is SR or NSR. If the FDA does not agree with an IRB's decision that a device study presents a NSR, an IDE application must be submitted to FDA. The FDA becomes informed of the NSR determination indirectly by the sponsor(s), who must file "abbreviated IDE requirements" {21 CFR 812.2(b).}

The PI is responsible for identifying the funding source in the initial submission. Reviewers will complete the appropriate checklist relating to the funding source to ensure criteria are met. RSC staff will work with reviewers to verify the checklists are complete and provide any additional assistance and guidance.