IO: Institutional Official; individual who is legally authorized to act for the institution and ensures the effective functioning of the IRB.

IRB: Institutional Review Board.

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually.

UWM: University of Wisconsin – Milwaukee.

The IRB has a Chair and one or more Vice Chairs. The Chair is a respected, active member of the faculty or staff of UWM, who is concerned about human rights and ethical issues. The Chair is knowledgeable about the application of regulations and ethical principles in human subject research. The Chair also leads the IRB meetings and facilitates communication between investigators and the IRB office staff. As a representative of the institution and the IRB, the Chair exhibits high standards of moral integrity and ethical conduct and sets an example for IRB members. The IRB Chair fosters an environment that encourages the free and full participation of all IRB members in its deliberations. The Vice Chair is considered a Chair-in-Training. As a representative of the institution and the IRB, the Vice Chair must exhibit high standards of moral integrity and ethical conduct. The Vice Chair leads IRB meetings in the Chair’s absence.

IRB Chair

1. Appointment process

• a. The IO solicits recommendations for the Chair from the IRB and IRB office staff. The IO consults with the IRB and the Vice Provost for Research and the Vice Chancellor of Finance and Administrative Affairs regarding the candidate(s) for Chair.
• b. Once approved by the IO and Vice Chancellors, the IRB office staff forwards the nomination to the Chancellor, who issues the appointment letter.
• c. The Chair formally accepts this role by signing and returning the Chancellor’s Letter of Appointment.

2. A Chair serves continuously without limit at the discretion of the IO.

3. The IO may remove an IRB Chair at any time, after consulting with the Vice Provost for Research, the Vice Chancellor of Finance and Administrative Affairs, the IRB office staff, and/or IRB members, as appropriate.

Vice Chair

1. Appointment Process

• a. The IO solicits recommendations from the IRB Chair and IRB office staff for a Vice Chair. The IO consults with the Vice Provost for Research and the Vice Chancellor of Finance and Administrative Affairs regarding the nominee(s) for Vice Chair.
• b. The IO determines the term length (one to three years).
• c. Once approved by the IO and Vice Chancellors, the IRB office staff forwards the nomination to the Chancellor, who issues the appointment letter.
• d. The Vice Chair formally accepts this role by signing and returning the Chancellor’s Letter of Appointment.

2. The Vice Chair’s term may be renewed at the discretion of the IO. There is no limit to the number of terms.

3. Whenever the Chair is not available, the Vice Chair assumes the responsibilities of the Chair during the period of absence or other unavailability.

4. The IO may remove an IRB Vice Chair at any time, after consulting with the IRB office staff and the IRB Chair.

Temporary Chair

If both the Chair and Vice Chair are unavailable, the IO may designate a temporary Chair. When feasible, the IO discusses the appointment of a temporary Chair with the IRB.

 101: IRB Membership

UWM IRB SOP 102: IRB Chair and Vice Chair (PDF)

CITI: Collaborative Institutional Training Initiative (CITI Program); an organization that provides web-based educational courses in research ethics, regulatory oversight, responsible conduct of research, research administration, etc.

HIPAA: Health Insurance Portability and Accountability Act of 1996; federal legislation relating to the privacy and security of medical records.

IRB: Institutional Review Board.

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually.

IRB members participate in both initial and continuing education.

These programs focus on:

•The ethical principles and regulatory requirements underpinning human subject protections.

•Applying those principles and requirements to the review of research.

Initial Education Program

The initial education program consists of in-person training provided by the IRB office staff and online training provided by CITI. All IRB Chairs, Vice Chairs, members, and alternates must complete the training in the following areas before actively participating in the IRB:

1. Ethical Principles and the Belmont Report

2. Regulatory Requirements

3. UWM Federal Wide Assurance (FWA)

4. UWM Institutional Policies and Procedures

5. IRB’s Role and Responsibilities

6. Application of the Principles and Regulations to the Initial and Continuing Review of Research and Modifications

7. Research Protocol Review Criteria and Review Process

8. Informed Consent Process and Document

9. Vulnerable Populations: Pregnant Women, Fetuses, Prisoners, Children and Others

10. Investigator Responsibilities

11. HIPAA Policies and Procedures In addition, new members are assigned to review at least one protocol along with an experienced member before reviewing protocols on their own.

Continuing Education Program

IRB members complete a CITI training course every 3 years, and the IRB office staff provides continuing education specifically for IRB members at least once annually. IRB members are also encouraged to take advantage of the following continuing education opportunities:

• Scheduled short current topics (case studies and current events)

• Just-in-Time training, in response to specific issues raised during the review of research protocols

• Regional and national educational conferences

• Training sessions for researchers offered by the IRB office staff

45 CFR § 160 (HIPAA)

45 CFR § 164 (HIPAA)

UWM IRB SOP 201: IRB Member Education (PDF)

CITI: Collaborative Institutional Training Initiative (CITI Program); an organization that provides web-based educational courses in research ethics, regulatory oversight, responsible conduct of research, research administration, etc.

GCP: Good Clinical Practice.

HIPAA: Health Insurance Portability and Accountability Act of 1996; federal legislation relating to the privacy and security of medical records.

IRB: Institutional Review Board.

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually.

NIH: National Institutes of Health.

PI: Principal Investigator.

SPI: Student Principal Investigator.

UWM: University of Wisconsin – Milwaukee.

To ensure that individuals conducting research with human subjects are sufficiently qualified to protect the safety and wellbeing of those subjects, researchers must complete training in human subjects protections on a regular basis. In addition to the required training, the IRB office staff offers a range of optional in-person or online training.

Scope The Required Training outlined below applies only to PIs and SPIs or other primary contacts on a study. For other research personnel, the PI determines what training is necessary for the individual’s specific role and ensures that it is completed.

The PI’s discretion regarding training is superseded when:

• Specific training is required by external funding agencies (e.g. GCP training for all key personnel on NIH-funded clinical trials); or

• The IRB determines that specific additional training is necessary to ensure the protection of human subjects and/or the scientific validity of the data. PIs are required to keep training records of all personnel working on their research studies and may be asked to provide these training records to the IRB.

Required Training

At the time of initial study submission, the IRB office staff verifies that the PI and SPI / primary contact have completed IRB CITI training within the last 3 years. Any one of the following UWM-specific CITI courses fulfills this requirement:

• IRB-Biomedical Researchers

• IRB-Biomedical and Social & Behavioral Combined Researchers

• IRB-Social & Behavioral Researchers

• IRB Members

• Refresher courses for any of the above.

CITI training completed through another institution may be accepted in lieu of the courses listed above, if the completed course is similar to the UWM required modules. IRB office staff make this determination. If the researcher has not completed CITI training within the last 3 years, the IRB office staff notifies the researcher that this needs to be completed.

• For exempt studies, approval may be issued in rare cases with CITI training incomplete at the discretion of the IRB office staff. Example: A student project where the SPI has completed CITI training and the faculty PI agrees to complete the training within the next month.

• For expedited and full board studies, IRB approval of the study is not issued until CITI training is complete and current.

GCP

GCP training is required for all key personnel on NIH-funded clinical trials, and strongly recommended for all key personnel on all other federally-funded clinical trials. Any one of the following CITI courses fulfills this requirement:

• GCP – Social and Behavioral Research Best Practices for Clinical Research

• GCP for Clinical Investigations of Devices

• GCP for Clinical Trials with Investigational Drugs and Medical Devices (US FDA Focus)

• Refresher courses for any of the above.

HIPAA

HIPAA training, available through UWM’s legal department, is strongly recommended for any PI or SPI using medical records in research.

Optional Education

1. The IRB office staff offers multiple in-person training sessions each year on a variety of topics. Researchers are encouraged to attend these sessions to learn more about a specific area of human subjects research, refresh current knowledge, and to ask questions.

2. Self-paced online training on select topics is available for researchers through the UWM IRB website.

45 CFR § 160 (HIPAA)

45 CFR § 164 (HIPAA)

UWM IRB SOP 202: Researcher Education (PDF)

HSR: Human Subjects Research, as defined in 45 CFR 46.

IO: Institutional Official

Individual who is legally authorized to act for the institution and ensures the effective functioning of the IRB.

IRB: Institutional Review Board.

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually.

The IRB office staff supports the IRB in the following ways:

• Protocol reviews

• Providing expertise in regulations and laws related to human subjects research

• Post-approval reviews

• Facilitating IRB meetings

• Administrative Functions The IRB office staff may be voting members of the IRB

Protocol Reviews

The IRB office staff receives and processes all submissions to the IRB and performs the initial review. This includes new studies, amendments, continuing reviews, reportable events, and requests for HSR determination. Where a primary reviewer is required, the IRB office staff assigns a reviewer from among the IRB members, in consultation with the Chair when necessary. For studies requiring review by the convened IRB, the IRB office staff places the submission on the next available meeting agenda. IRB office staff serve as non-compliance subcommittee members when reports of noncompliance are received. They may be tasked with investigating details of instances of non-compliance so that the subcommittee and/or the IRB may make an informed decision.

Regulatory Expertise

The IRB office staff regularly participates in continuing education, ensuring that UWM IRB remains aware of current thought and changes in regulations related to human subjects research. The IRB office staff shares this knowledge and expertise with IRB members and researchers through formal in-person training sessions, guidance documents, communications with the research community about new events or changes, and individual consultation on questions or concerns researchers and members may have.

Post-Approval Reviews

The IRB office staff schedules and conducts post-approval reviews to ensure compliance with the appropriate regulations and the approved protocol.

Facilitating IRB Meetings

The IRB office staff schedules IRB meetings, records member attendance, monitors to ensure quorum is maintained, documents the IRB’s decisions and discussion, and creates the meeting agenda and minutes. The IRB office staff notifies investigators of the IRB’s decisions and any conditions or stipulations of approval. The IRB may designate the IRB office staff to review requested revisions and determine that all conditions of approval are met.

Administrative Functions

The IRB office staff maintains all required records for individual studies until at least 3 years past the end date of the study, or longer if required by regulations. The IRB office staff also maintains all records of IRB meetings in accordance with Wisconsin open records laws and federal regulations. The IRB office staff maintains and updates the IRB website as needed, creates and updates SOPs, and publishes and disseminates important communications to IRB members and the research community. The IRB office staff arranges reliance agreements with other institutions, in cooperation with the IO.

45 CFR 46.102 Wis. Stats.

§§ 19.21-19.39 (Wisconsin open records law)

SOP 201 – IRB Member Education SOP 202 – Researcher Education

SOP 302 – Record Retention

SOP 303 – IRB Meetings

SOP 401 – Review of Research

SOP 309 – Compliance and Post-Approval Reviews

UWM IRB SOP 301: Role of the IRB Staff (PDF)

FDA: Food and Drug Administration; the division of HHS that oversees drugs, medical devices, and food.

HHS: Health and Human Services; a department of the US government whose responsibility is the protection of the health of Americans

IRB: Institutional Review Board

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually

OHRP: Office of Human Research Protections; a division of HHS that oversees human subjects research

PI: Principal Investigator

SPI: Student Principal Investigator

UWM: University of Wisconsin – Milwaukee

The Principal Investigator and IRB must maintain and retain the appropriate records for each research study, consistent with federal regulations, Wisconsin open meeting laws, and UWM’s records retention policies. Records must be maintained in a confidential and secure manner. IRB records are generally subject to open records requests.

Exceptions:

• Minutes of closed session IRB meetings

• Student research projects

• Any other documents created by or related to a student

Principal Investigator Record Retention

Each Principal Investigator must retain records of all correspondence relating to the use of human subjects in research, as required by UWM procedures and federal regulations.

This includes:

• All IRB application materials (initial, amendment, continuing review, etc.)

• All approval letters and important correspondence (initial, continuing review, and amendment approval letters; reportable event memos, etc.)

• All versions of approved informed consent forms

• Training records for research team members

• Research data, which must be stored according to the IRB approved protocol Records of human subject research may be inspected by federal authorities, the IRB, and/or accreditation agencies. Research records must be kept for a minimum of three years after completion of the study. For studies that involve drugs or devices seeking FDA approval, records must be kept for three years after the FDA has taken final action on the marketing application. Other requirements for record retention may also apply. Funding agency, department, professional field, or other UWM requirements may be different. Records should be maintained in a manner compliant with the most stringent of all applicable requirements.

Researchers Leaving UWM

If a researcher leaves UWM, appropriate arrangements should be made for the care and retention of the records. This may include transfer of oversight of the data to another UWM faculty or staff member, de-identification or destruction of data, or transfer of the data to a new institution. All actions related to transfer of data to another institution must be discussed with appropriate parties within both UWM and the receiving institution, including the IRBs of both institutions.

IRB Record Retention

The IRB maintains records of all protocols and correspondence submitted to the IRB and minutes from all full board meetings for a minimum of three years after completion of the study. All records are accessible for inspection and copying by authorized representatives of OHRP, HHS, FDA, Sponsors, university officials, and internal auditors at reasonable times and in a reasonable manner.

45 CFR 46.115 21 CFR 56.115 Wis. Stats.

§§ 19.21-19.39 (Wisconsin open records law) Wis.

Stats. §§ 19.81-19.98 (Wisconsin open meetings law)

UWM IRB SOP 302: Record Retention(PDF)

IRB: Institutional Review Board

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually

IRB members convene regularly to review protocols involving human subjects. The IRB reviews all research protocols at convened meetings where a quorum has been established, except where an application is eligible for exempt or expedited review. The IRB office staff prepares minutes of each meeting to document the IRB’s review of research protocols, policy discussions, and continuing education.

Investigators and Guests

The IRB may invite investigators and/or research team members to attend the IRB meeting. This allows IRB members to ask questions and clarify information. The IRB complies with the State of Wisconsin open meeting regulations. If a member requests that the IRB go into closed session, investigators and other guests will be asked to leave the room unless invited by the Chair to remain. The Chair will call for a motion to go into closed session.

Confidentiality

IRB members, staff, and guests are reminded a teach meeting to maintain confidentiality of the IRB’s discussions and decisions.

Meeting scheduling

The IRB generally meets monthly, but may meet more or less often as needed. IRB office staff set the dates for meetings and contact members to ensure there will be quorum at the meeting. IRB office staff conduct a pre-review of all submissions and determine the level of review required, consulting with IRB members or the Chair when necessary. All protocols deemed either to involve more than minimal risk or that require full board review for regulatory compliance (e.g. device studies where a “non-significant risk” determination is required), are placed on the next available meeting agenda.

Materials

Members receive the meeting agenda and all submitted materials for each full board review. The agenda includes:

•Research protocols for full board review

•Research that has been approved through exempt or expedited review procedures (including new submissions, amendments, continuing reviews, and reportable events)

•Research deferred to other institutions

•Post-approval reviews conducted Submitted materials for full board reviews include: •Study protocol

•Informed consent and assent documents

•Recruitment materials

•Data collection tools

•Any other documents deemed necessary or helpful for the review.

IRB office staff distribute the meeting materials at least 4 days before the meeting. This allows members sufficient time to review the materials and to contact investigators with questions if they choose.

Quorum, Meeting Procedures, and Voting

A quorum is defined as greater than 50% of the voting membership, including at least one member whose primary concerns are in nonscientific areas. Voting members may attend meetings by teleconference or videoconference if:

1.They have received all items for review in advance of the meeting; AND

2.The equipment permits meaningful participation in discussion and voting. A scientist and non-scientist must be present at each meeting. In order to in initiate a vote, a motion must be made by a voting member of the IRB and seconded. When a motion is not seconded, it does not go forward to a vote. Any motion that is seconded must go forward for a vote unless the person who made the motion withdraws it. If a motion does not pass, then the Chair will ask for another motion, and so on, until a motion passes or is withdrawn. The approval of IRB actions requires the vote of a simple majority (greater than 50%) of the voting members present at the meeting. Only IRB members who attend the meeting may vote. Members who are unable to attend may submit written comments or questions prior to the meeting, but do not vote.

Minutes

The minutes are recorded in sufficient detail to document the following:

•IRB Member attendance and the presence of any invited investigators or guests. •Motions to go into closed session, the reasons for doing so, the applicable statutory exemptions for closed sessions, and the board’s vote on such motions.

•IRB committee acknowledgement of expedited and exempt reviews.

•Summary of the discussion and controverted issues for each research protocol reviewed.

•Decisions reached and any required modifications.

•Votes on the decisions, including a tally of votes for, against, and abstaining for each vote, and recusal of members due to conflicting interests.

•Reasons for requiring modifications to secure approval of a research protocol, for disapproving a research protocol, or suspending or terminating a research protocol.

•Documentation that a waiver or alteration of informed consent or a waiver of documentation of informed consent, if granted, is appropriate.

•The level of risk involved in the research.

•The review frequency for the next continuing review, if less than one year.

•For studies determined to be minimal risk, whether or not continuing review will be required.

•Policy discussions

•Any continuing education provided during a meeting Members receive a copy of the minutes for review prior to the next meeting. Suggested modifications to the minutes are discussed at a full board meeting and agreed to by consensus, and the IRB staff modifies the minutes according to the IRB’s recommendations.

Wis. Stats. §§ 19.81-19.9845

CFR §§46.108, 46.11521

CFR §§56.108, 56.115

102: IRB Chair and Vice Chair

UWM IRB SOP 303: IRB Meetings(PDF)

COI: Conflict of Interest

IRB: Institutional Review Board

PI: Principal Investigator

SPI: Student Principal Investigator

UWM: University of Wisconsin-Milwaukee

Researchers inherently have a conflict of interest in their research proposals, as the research frequently has a direct impact on the researcher’s professional or academic career. Additionally, successful completion of research proposals is vital to tenure, promotion, publication, and completion of degrees. In some cases, researchers may also have a financial conflict of interest in the outcome of the research. IRB members may have a conflict of interest due to their involvement as a researcher in a protocol under review, due to personal or professional relationships with the researcher(s), or due to a financial interest in the proposed research. UWM may have an institutional conflict of interest when the institution is better or worse off depending on the outcome of the research. The IRB has the responsibility to ensure that these potential conflicts of interest do not negatively impact the rights or welfare of participants, or the fair and unbiased review of research proposals.

A Conflict of Interest occurs whenever an individual has incentive to act in a way to put their own personal or professional interests ahead of ethical considerations. COI also occurs when there is any appearance that an individual’s actions may be biased. A COI may be personal, professional, or financial. Identification of a potential COI does not confer any judgment about the moral character of the person identified to have a COI, but rather recognizes that the opportunity for biased conduct or wrongdoing exists. Measures taken to manage these COIs vary with the degree and type of COI.

Researcher COI

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research asserted that “investigators are always in positions of potential conflict by virtue of their concern with the pursuit of knowledge as well as the welfare of the human subjects of their research.” (1978). This inherent COI exists in all studies, and may or may not require any special management to ensure the protection of participants’ rights and welfare. Examples of other COIs may occur in studies where the researcher:

• Stands to accrue a significant financial benefit from the research (e.g. devices that may be patented and/or sold for a profit if successful)

• Has a relationship with the potential participants (e.g. instructors recruiting their own students) In each protocol review, the IRB notes any potential COI that could impact the rights or welfare of participants, and may require additional safeguards to minimize this impact. For research involving entities for which the PI has a financial COI disclosed to the university, the PI must have a COI management plan reviewed and approved by the UWM COI committee and a copy should be shared with the UWM IRB for relevant studies. Examples of potential actions the IRB may take to manage COIs:

• Require that the researcher disclose the COI to participants (typically in the informed consent document)

• Require that the researcher with the COI not participate in participant recruitment or consent activities

• Require the inclusion of an unbiased co-investigator on the study team

• Observe or monitor the consent process Investigators may choose to manage their own COI. Examples of self-management may include:

• Having someone else conduct the research

• Divesting financial interests

IRB Member COI

COIs may exist in studies where the IRB member:

• Is the PI or a co-investigator

• Is the faculty member overseeing a SPI’s project

• Has a personal relationship (either positive or negative) with any member of the study team, such that the member feels it may be difficult to provide an unbiased review

• A power differential exists (e.g. the researcher is Chair of the IRB member’s department)

• May benefit financially from the study in some way

• Believes for any other reason that they are unable to perform an objective review, or that others may perceive the review as biased. Managing COI in Studies Undergoing Full Board Review

• IRB members must disclose any known potential COI to the Chair at the start of the IRB meeting.

• IRB members do not vote on research protocols in which they may have conflicting interests.

• The member may be asked to recuse (leave the room) for the duration of the discussion and vote on that research protocol if the member’s presence could create a bias. Managing COI in Studies Undergoing Expedited Review

• IRB members will not be assigned as expedited reviewers for any study where there is an obvious COI.

• If an IRB member is assigned to review a study for which they have a COI, the member must notify IRB office staff and request that the study be assigned to a different reviewer. The member may simply state that they are unable to review the protocol, and do not need to disclose the nature of the COI to the IRB office staff.

Institutional COI

To manage institutional conflicts of interest, the IRB functions independently from the university as an independent board whose determinations are not dictated or influenced by anyone outside the IRB. Upper-level administrators may not be voting members of the IRB, and do not attend meetings where there may be an institutional COI. The potential for hierarchical COI for the IRB office staff is also present. This COI is managed by having an organizational structure where the IRB office is not under any department or division charged with promoting or bringing additional research to campus, but is instead a part of University Safety and Assurances, under the Division of Finance and Administrative Affairs. If these structural measures are not sufficient to manage an institutional conflict of interest for a specific protocol, other measures may be implemented, such as hiring an external IRB to review and oversee the conduct of the study, or hiring an external individual or organization to conduct the research.

45 CFR 46.107

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Report and recommendations: Institutional review boards (DHEW[OS]78-00008). Washington, DC: Department of Health, Education, and Welfare; 1978.

UWM IRB SOP 304: Conflicts of Interest(PDF)

CFR: Code of Federal Regulations

FDA: Food and Drug Administration

FERPA: Family Educational Rights and Privacy Act

Full board: A convened meeting of the IRB at which a quorum of members is present

HIPAA: Health Insurance Portability and Accountability Act

IO: Institutional Official

IRB: Institutional Review Board

Minimal risk: 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.

PI: Principal Investigator

UWM: University of Wisconsin – Milwaukee

For all review of research, the IRB bases its determinations on upholding the Belmont principles of Respect for Persons, Justice, and Beneficence, as well as complying with all applicable federal and state laws and university policies.

Regulations

In order to approve a new research protocol involving human subjects, the IRB must determine that all of the criteria from 45 CFR § 46.111 are satisfactorily met:

1. Risks to subjects are minimized by using procedures that are consistent with sound research design and that do not unnecessarily expose subjects to risk, and whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

2. 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 from the research.

3. Selection of subjects is equitable. In making this assessment the IRB takes into account the purposes of the research and the setting in which the research will be conducted. The IRB is particularly cognizant of the special problems of research that involves subjects who are vulnerable to coercion or undue influence, such as children, prisoners, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons.

4. Informed consent will be sought from each prospective subject or their legally authorized representative, as required by §46.116

5. Informed consent will be appropriately documented or appropriately waived in accordance with §46.117.

6. When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

7. When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data. For research that falls under the purview of the FDA, the IRB determines that the criteria from 21 CFR § 56.111 are met. For research that is not federally funded or subject to FDA oversight, the IRB may use flexible policies in granting exceptions to the requirements of 45 CFR 46 when deemed appropriate.

Risk Level

Research involving more than minimal risk must be reviewed by the IRB at a convened meeting (“full board” review). Research involving minimal risk that fits into one or more expedited or exempt review categories may be reviewed by a designated IRB reviewer rather than by the full IRB.

Compliance

Principal Investigators must not start any aspect of research involving human subjects (e.g., recruitment, screening, etc.) until they have received written notification of IRB approval. The PI is responsible for compliance with other laws and institutional rules (such as compliance with HIPAA, FERPA, biosafety regulations, etc.) and must provide the documentation of any other reviews to the IRB upon request.

Communication

The IRB communicates all its findings and actions to the PI and notifies the Institutional Official in writing. When projects are federally funded, the PI is responsible for sending a copy of the approval letter to the Grants and Contracts Office and/or the funding agency, as needed.

Review Process for New Research Protocols

Principal Investigators who intend to conduct research involving human subjects must submit a research protocol and any other supporting documentation to the IRB for review and approval using the designated electronic system. Upon receipt of a new protocol submission, the IRB office staff conducts an initial review. The office staff determines the review level required (Exempt, Expedited, Full Board, or Not Human Subjects Research). Depending on the review level and completeness of the submission, IRB office staff may either request revisions or process the submission to the next stage of review

Exempt Review

Certain types of research protocols may be eligible for review under exempt review procedures. The research must involve no more than minimal risk and fit one or more of the categories for exempt research as outlined in 45 CFR §46.104(d). IRB office staff review the protocol and may assign an IRB member as an additional reviewer if needed. IRB office staff work with the PI until the study satisfactorily meets the same requirements for approval as expedited and full board studies. The IRB office staff then notify the PI of this approval in writing. Exempt studies are generally required to follow 45 CFR 46, but flexibility in compliance with these regulations is left to the discretion of IRB office staff and/or reviewing IRB member, who may waive one or more requirements when such a waiver does not negatively impact the rights or welfare of human subjects.

Limited IRB Review

Certain exempt studies may qualify for exemption only with a “limited IRB review”. For this type of review, the IRB will make the following determination(s):

• For Exempt categories 2, 3, or 8, where the information is recorded by the investigator in such a manner that the identity of the human subject can readily be ascertained, directly or through identifiers linked to the subjects; or for secondary research for which broad consent is required, the IRB will make the following determination as required by § 46.111(7):

1. There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

• For Exempt category 7, the IRB will make the following determinations as required by §46.111(8):

2. Broad consent for storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens is obtained in accordance with the relevant requirements in § 46.116;

3. Broad consent is appropriately documented, or a waiver of documentation is appropriate;

4. If there is a change made for research purposes in the way the information specimens are stored or maintained, that there are adequate provisions to protect the privacy of subjects and maintain the confidentiality of the data;

5. When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

Expedited Review

Certain types of research protocols may be eligible for review under expedited review procedures as governed by 45 CFR 46.110. The research must involve no more than minimal risk and fit one or more of the categories for expedited review procedures as specified in the Federal Register. IRB office staff complete an initial review of the study submission and will assign one or more reviewers from among the IRB members, in consultation with the Chair when needed. IRB members are assigned to review research protocols based on the nature of the research and the expertise of the IRB member. IRB office staff may act as the sole reviewer if they feel they have adequate expertise to complete the review without input from additional reviewers. Examples: research involving only records review, or where study procedures involve extremely low or no risk. Assigned IRB members review the research application and all supporting materials to determine whether the research:

1. Meets the definition of minimal risk,

2. Meets the criteria of one or more of the eligible categories, and

3. Fulfills the regulatory criteria for approval This determination is documented in reviewer checklists and/or notes in the electronic submission system. IRB members reviewing a study may:

• Ask questions about the research,
• Require modifications to the protocol and other study materials, • Recommend approval,
• Request additional IRB members to review the protocol, or
• Request that the study be reviewed by the full board. Reviewers may not disapprove a study via expedited procedures; disapproval may only occur by a majority vote at a convened IRB meeting. If the reviewer recommends disapproval, the study must be referred to the full board for review. If there are multiple expedited reviewers and their determinations conflict, IRB office staff communicates with the members to determine whether concordance can be reached. If not, the IRB Chair also reviews the research protocol and may either make the final decision or refer the matter to the full board for review. The IRB office staff communicate the determinations of the IRB in writing to the investigator(s). If instructed by the IRB member(s) that reviewed the study, IRB office staff may review submitted revisions.

Full Board Review

The IRB office staff completes an initial review and may either:

• Request clarifications or additional documents, or
• Place the study on the next available meeting agenda IRB office staff assigns one or more IRB members as primary reviewers, based on the nature of the research and the expertise of the IRB member. Primary reviewers are encouraged to contact the PI to ask questions or seek clarification about the research prior to the full board meeting. Each IRB member receives the protocol and all supporting documents prior to the meeting. Investigators are invited to attend the meeting at which their protocol will be reviewed. If present, a researcher will be asked to describe the research project, and the IRB will ask any questions or request clarifications about the study. After sufficient discussion, the members vote on each research protocol and the votes are recorded in the meeting minutes. The full board IRB may make the following determinations:

1. Approved: Approve as submitted.

2. Approved with Conditions:

• The study meets regulatory criteria for approval, as long as the specified conditions are met. The IRB may grant either the primary reviewer(s) or IRB office staff the authority to review the revisions to ensure compliance with the conditions required by the IRB.

3. Tabled: Table the discussion of the research because additional information and/or protocol revisions are required.

4. Disapproved: The research protocol cannot be approved as proposed. The IRB’s determinations are documented in reviewer checklist(s) and in the IRB meeting minutes. The decisions will be based on the votes of the majority (more than 50%) of the voting members present at a full board IRB meeting.

Communication of IRB Findings and Actions to the Investigator and the Institution

IRB office staff communicate the IRB’s findings and actions to investigators and the Institution in writing and retain copies of these communications in the study’s files. All expedited and exempt reviews are noted on the next available IRB meeting agenda and documented in the IRB meeting minutes. This inclusion serves as documentation of the reviews that have been completed and notification to the full IRB. This notification does not require action by the convened IRB. However, the IRB may raise questions about any research that was previously acknowledged under exempt or expedited procedures. All meeting minutes are sent to the IO and made available to others within the institution upon request.

Expiration dates

Full board studies: The approval period begins the date of the convened meeting at which the IRB voted to approve the study or approve with conditions. The default approval period is one year, but the IRB may determine that a shorter review period is appropriate.

Example 1: The IRB votes to approve a study with conditions on October 5, 2019. The expiration date will be October 4, 2020, regardless of how long it takes the PI to make the IRB’s requested revisions.

Example 2: The IRB votes to approve a study with conditions on October 5, 2019, but grants only a 6-month approval period. The expiration date will be April 4, 2020, regardless of how long it takes the PI to make the IRB’s requested revisions Expedited studies receive a one-year approval, beginning on the date IRB office staff determine that any conditions for approval have been met and issue the approval letter.

Example 3: The reviewers complete a review on February 18, 2020 and require revisions. The PI submits the revised materials March 3. IRB office staff review these revisions March 7, determine the revisions are acceptable, and issue the approval letter. The approval date is March 7, 2020, and the study’s IRB approval will expire March 6, 2021. Exempt studies receive a 3-year approval, beginning the date IRB office staff issues the approval letter.

45 CFR 46 21 CFR 56 (FDA)

45 CFR 164 (HIPAA)

34 CFR 99 (FERPA)

UWM IRB SOP 401: Initial Review of Research (PDF)

Certain types of minimal risk research, which fall under one or more categories of exempt research as outlined in 45 CFR § 46.104 (d), qualify for Exempt review:

1. Research, conducted in established or commonly accepted educational settings, that specifically involves normal educational practices that are not likely to adversely impact students’ opportunity to learn required educational content or the assessment of educators who provide instruction. This includes most research on regular and special education instructional strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

2. Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording) if at least one of the following criteria is met:

• (A) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;
• (B) Any disclosure of the human subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation; or
• (C) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by §46.111(a)(7).

3. Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection and at least one of the following criteria is met:

• (A) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;
• (B) Any disclosure of the human subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation; or
• (C) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by §46.111(a)(7). For the purpose of this provision, benign behavioral interventions are brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the subjects, and the investigator has no reason to think the subjects will find the interventions offensive or embarrassing. Provided all such criteria are met, examples of such benign behavioral interventions would include having the subjects play an online game, having them solve puzzles under various noise conditions, or having them decide how to allocate a nominal amount of received cash between themselves and someone else.
• (D) If the research involves deceiving the subjects regarding the nature or purposes of the research, this exemption is not applicable unless the subject authorizes the deception through a prospective agreement to participate in research in circumstances in which the subject is informed that he or she will be unaware of or misled regarding the nature or purposes of the research.

4. Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable bio-specimens, if at least one of the following criteria is met:

• (A) The identifiable private information or identifiable bio-specimens are publicly available;
• (B) Information, which may include information about bio-specimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;
• (C) The research involves only information collection and analysis involving the investigator’s use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164, subparts A and E, for the purposes of “health care operations” or “research” as those terms are defined at 45 CFR 164.501 or for “public health activities and purposes” as described under 45 CFR 164.512(b); or
• (D) The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for non-research activities, if the research generates identifiable private information that is or will be maintained on information technology that is subject to and in compliance with section 208(b) of the E-Government Act of 2002, 44 U.S.C. 3501 note, if all of the identifiable private information collected, used, or generated as part of the activity will be maintained in systems of records subject to the Privacy Act of 1974, 5 U.S.C. 552a, and, if applicable, the information used in the research was collected subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.

5. Research and demonstration projects that are conducted or supported by a Federal department or agency, or otherwise subject to the approval of department or agency heads (or the approval of the heads of bureaus or other subordinate agencies that have been delegated authority to conduct the research and demonstration projects), and that are designed to study, evaluate, improve, or otherwise examine public benefit or service programs, including procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs. Such projects include, but are not limited to, internal studies by Federal employees, and studies under contracts or consulting arrangements, cooperative agreements, or grants. Exempt projects also include waivers of otherwise mandatory requirements using authorities such as sections 1115 and 1115A of the Social Security Act, as amended.3

• (A) Each Federal department or agency conducting or supporting the research and demonstration projects must establish, on a publicly accessible Federal Web site or in such other manner as the department or agency head may determine, a list of the research and demonstration projects that the Federal department or agency conducts or supports under this provision. The research or demonstration project must be published on this list prior to commencing the research involving human subjects.

6. Taste and food quality evaluation and consumer acceptance studies:

• (A) If wholesome foods without additives are consumed, or
• (B) If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

7. Storage or maintenance for secondary research for which broad consent is required: Storage or maintenance of identifiable private information or identifiable bio-specimens for potential secondary research use if an IRB conducts a limited IRB review and makes the determinations required by §46.111(a)(8).

8. Secondary research for which broad consent is required: Research involving the use of identifiable private information or identifiable bio-specimens for secondary research use, if the following criteria are met:

• (A) Broad consent for the storage, maintenance, and secondary research use of the identifiable private information or identifiable bio-specimens was obtained in accordance with §46.116(a)(1) through (4), (a)(6), and (d);
• (B) Documentation of informed consent or waiver of documentation of consent was obtained in accordance with §46.117;
• (C) An IRB conducts a limited IRB review and makes the determination required by §46.111(a)(7) and makes the determination that the research to be conducted is within the scope of the broad consent referenced in paragraph (d)(8)(i) of this section; and (iv) The investigator does not include returning individual research results to subjects as part of the study plan. This provision does not prevent an investigator from abiding by any legal requirements to return individual research results.

UWM IRB Appendix 401.1: Exempt Review Categories(PDF)

Certain types of research protocols may be eligible for review under expedited review procedures as governed by 45 CFR 46.110. The research must involve no more than minimal risk and fit one or more of the categories for expedited review procedures as specified in the Federal Register. There are nine categories of research eligible for expedited review procedures. These categories are described below:

1. Clinical studies of drugs and medical devices only when condition (a) or (b) is met.

• (a) Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.)
• (b) Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

2. Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

• (a) from healthy, non-pregnant adults who weigh at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in an eight-week period and collection may not occur more frequently than two times per week; or
• (b) from other adults and children, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an eight-week period and collection may not occur more frequently than two times per week.

3. Prospective collection of biological specimens for research purposes by noninvasive means. Examples:

• (a) hair and nail clippings in a non disfiguring manner;
• (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction;
• (c) permanent teeth if routine patient care indicates a need for extraction;
• (d) excreta and external secretions (including sweat);
• (e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue;
• (f) placenta removed at delivery;
• (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor;
• (h) supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques;
• (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; or
• (j) sputum collected after saline mist nebulization.

4. Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.) Examples:

• (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject’s privacy;
• (b) weighing or testing sensory acuity;
• (c) magnetic resonance imaging;
• (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; or
• (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

5. Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for non-research purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR § 46.101(b)(4). This listing refers only to research that is not exempt.)

6. Collection of data from voice, video, digital, or image recordings made for research purposes.

7. Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR §§ 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)

8. Continuing review of research previously approved by the convened IRB as follows:

• (a) where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or
• (b) where no subjects have been enrolled and no additional risks have been identified; or
• (c) where the remaining research activities are limited to data analysis.

9. Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where Categories 2 through 8 do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

UWM IRB Appendix 401.2: Expedited Review Categories (PDF)

CFR: Code of Federal Regulations

IRB: Institutional Review Board

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually

OHRP: Office of Human Research Protections; a division of HHS that oversees human subjects research

Subject: For the purposes of this SOP, “Subject” refers to the subject and/or the subject’s legally authorized representative. “Subject” may also be used interchangeably with “Participant”.

UWM: University of Wisconsin – Milwaukee

The Belmont principle of Respect for Persons requires that potential subjects, to the degree that they are capable, be given the opportunity to choose what shall happen to them. Before involving a human subject in research, an investigator must obtain the subject’s informed consent. The IRB reviews the informed consent process and documents that Principal Investigators will use to ensure that research subjects are adequately informed about the research before agreeing to participate. The IRB has the authority to observe or have a third party observe the consent process and the research at any time. Under certain circumstances, the IRB may waive the requirement to obtain or document informed consent or may approve an alteration of informed consent. In cases in which the signed consent requirement is waived, the IRB may still require the Principal Investigator to provide subjects with a written statement regarding the research.

Informed Consent Process

Informed consent is a process that begins with recruitment and continues throughout the study until all activities are complete. The participant should receive sufficient information to provide consent, and must be told if any new developments occur that might affect their willingness to participate. Participants must retain the ability to withdraw from the research at any point, with no negative consequences. Researchers should avoid any appearance of coercion or pressure to participate in the consent process. For studies where there is a power differential, such as an instructor recruiting their own students, it may be appropriate to have someone else on the research team conduct the consent discussion. After the study is complete, the consent process may still continue. In some studies, it’s appropriate to allow a participant to review the research results before publication and choose to remove their data at that point. This is particularly important when an individual or community may be identifiable based on details in the final publication or presentation, to prevent harms to the participant’s or community’s reputation.

Informed Consent Requirements

UWM generally follows the consent requirements outlined at 45 CFR 46 for all research, unless another agency’s requirements apply (e.g. FDA requirements of 21 CFR 50).

1. An investigator shall seek informed consent only under circumstances that provide the prospective subject sufficient opportunity to discuss and consider whether or not to participate. The consent discussion must occur in such a way that minimizes the possibility of coercion or undue influence.

2. The information must be in language understandable to the subject.

3. The prospective subject must be provided with the information that a reasonable person would want to have in order to make an informed decision about whether to participate. They must also be given an opportunity to discuss that information.

4. Informed consent must present information in sufficient detail and must be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject’s understanding of the reasons why one might or might not want to participate.

5. No informed consent may include any exculpatory language. Exculpatory language is that through which the subject is made to waive, or appears to waive, any legal rights. This also includes language that releases, or appears to release, the investigator, sponsor, institution, or its agents from liability for negligence. All informed consent documents must contain the following elements of informed consent, except when the IRB has approved an alteration to these requirements:

• Statement that the study involves research and an explanation of the purposes of the research
• The expected duration of the subject’s participation
•  Description of the procedures to be followed and identification of any procedures which are experimental
• Description of any reasonably foreseeable risks or discomforts to the subject
• Description of any benefits to the subject or to others which may reasonably be expected
• Disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject
• Statement describing the extent to which confidentiality of records identifying the subject will be maintained
• For research involving more than minimal risk, an explanation as to whether any compensation and any medical treatments are available if injury occurs, and if so, what they consist of, or where further information may be obtained
• Research, Rights or Injury: An explanation of whom to contact for answers to questions about the research and research subjects’ rights, and whom to contact in the event of a research related injury
• Statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled
• Informed consent must begin with a concise and focused presentation of the key information most important for helping a potential subject decide whether to participate.
• The UWM IRB interprets this requirement to apply only to longer consent documents, and defines “longer” as more than 4 pages. Informed consent documents that are 4 pages or less do not need to contain this summary at the beginning.

One of the following: Statement that identifiers might be removed from the data or bio-specimens, and, after this de-identification, the data or bio-specimens could be used for future research studies or distributed to another investigator without additional informed consent; OR

1. Statement that the subject’s data or bio-specimens will not be used or distributed for any future research, not even if de-identified. The following additional elements must be included when the IRB deems them appropriate:
2. Statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant), which are currently unforeseeable

• Anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject’s consent

• Any additional costs to the subject that may result from participation in the research • The consequences of a subject’s decision to withdraw from the research and procedures for orderly termination of participation by the subject

• Statement that significant new findings developed during the course of the research, which may relate to the subject’s willingness to continue participation, will be provided to the subject

• The approximate number of subjects involved in the study

• Statement that the subject’s bio-specimens may be used for commercial profit, and whether the subject will or will not share in this profit

• Statement regarding whether clinically relevant research results will be disclosed to subjects, and if so, under what circumstances

• For research involving bio-specimens, whether the research will or might include whole genome sequencing Waiver to Obtain Informed Consent and Alterations of Informed Consent The IRB may waive or alter the requirement to obtain informed consent, if the IRB finds and documents that one of the sets of criteria below are met.

A. Public benefit or service programs: A1. The research or demonstration project is to be conducted by or is subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and A2. The research could not practicably be carried out without the waiver or alteration. OR

B. All other research: B1. The research involves no more than minimal risk to the subjects; B2. The research could not practicably be carried out without the waiver or alteration; B3. If the research involves using identifiable private information or identifiable bio-specimens, the research could not practicably be carried out without using such information or bio-specimens in an identifiable format; B4. The waiver or alteration will not adversely affect the rights and welfare of the subjects; and B5. Whenever appropriate, the subjects are provided with additional pertinent information after participation. OR

C. Screening, recruiting, or determining eligibility The IRB may approve a research proposal in which an investigator will obtain information or bio-specimens without informed consent for the purpose of screening, recruiting, or determining the eligibility of prospective subjects if either of the following conditions are met: C1. The investigator will obtain information through oral or written communication with the prospective subject or legally authorized representative; or C2. The investigator will obtain identifiable private information or identifiable bio-specimens by accessing records or stored identifiable bio-specimens

Waiver to Document Informed Consent

An IRB may waive the requirement for the Principal Investigator to obtain a signed consent form for some or all subjects, if one or more of the following conditions exist:

1. The only record linking the subject and the research would be the consent document, and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject’s wishes will govern. OR

2. The research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. OR

3. The subjects are members of a distinct cultural group or community in which signing forms is not the norm, the research presents no more than minimal risk of harm to subjects, and there is an appropriate alternative mechanism for documenting that informed consent was obtained.

Parental Consent and Waivers of Parental Consent

For the purposes of this section, “parent” refers to parents or legal guardians of minors. As a general rule, parents are in the best position to protect their children’s best interests, and should be given the opportunity to decide whether or not their child should participate in research. Waivers of parental permission are granted only if:

• The research is educational in nature, AND qualifies for Exempt category 1, AND the participation of all students is necessary to the aims of the research; OR
• The criteria for waiver of consent as outlined above are met; OR

All of the following criteria from 45 CFR 46.408 are met:

• The IRB determines that a research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children).
• An appropriate mechanism for protecting the children who will participate as subjects in the research is substituted. The choice of an appropriate mechanism would depend upon the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the research subjects, and their age, maturity, status, and condition. o The waiver is not inconsistent with Federal, state or local law.

45 CFR §§ 46.116, 46.117, 46.408 21

CFR 50 OHRP

Guidance: Informed Consent Tips (1993)

UWM IRB SOP 403: Recruitment Materials (PDF)

FDA: Food and Drug Administration; the division of Health and Human Services that oversees drugs, medical devices, and food.

IRB: Institutional Review Board

UWM: University of Wisconsin – Milwaukee

Recruitment is the first step in the consent process and requires IRB oversight. Materials developed for the sole purpose of recruiting human participants for research activities must be reviewed and approved by the IRB. It is recommended that the materials include the UWM protocol number and IRB approval date. The materials should be submitted with all formatting, pictures, etc. included. The IRB evaluates not only the written content, but the overall presentation for appropriateness and to ensure the recruitment material does not unduly promote compensation or promise benefit.

Submission Process

All recruitment materials must be submitted in an electronic format for the IRB’s review and approval. This includes not only the traditional ads or flyers, but also all scripts for all in-person, phone, and email recruitment. To the extent possible, the submission should include the final, formatted version of all materials, including font color and sizes, pictures, and any other visual effects. For audio or video recordings, researchers are required to submit the written text for review and approval. Once the wording has been finalized, it is recommended that an audio or video file also be submitted for review and for the IRB’s records. Copies of all approved recruitment materials will be stored in the study’s file in the online submission system. Alterations to the approved recruitment materials must be submitted to the IRB as a protocol amendment before use.

Content of Recruitment Materials

The IRB reviews the recruitment material to ensure that it accurately reflects the study, does not include excessive emphasis on compensation, and does not promise a certainty of benefit beyond what is outlined in the consent and the protocol. This is especially critical when a study may involve subjects who are likely to be vulnerable to undue influence. Generally, materials to recruit subjects should be limited to the information the prospective participants need to determine their eligibility and interest. When appropriately worded, the following items may be included in recruitment materials. However, not all of the listed items are required for every study.

• The study title;

• The condition under study and/or the purpose of the research;

• Basic eligibility criteria;

• A brief list of direct participation benefits, if any (e.g., a no-cost health examination); • the time or other commitment required of the subjects;

• The name and contact information of the researcher

• For research occurring in a specific location, the location name and/or address where the research will occur; and

• The IRB study number and approval date. To prevent undue influence, the following should not be included in recruitment materials:

• If an experimental drug or device is being studied, no claims should be made, either explicitly or implicitly, that it is safe or effective for the purposes under investigation, or that the test article is known to be equivalent or superior to any other drug or device.

• Recruitment for an experimental intervention should not use the term “new” without explaining that the intervention is investigational. A phrase such as “receive new treatments” leads study subjects to believe they will be receiving newly improved products of proven worth.

• Recruitment materials should not promise “free treatment,” when the intent is only to say subjects will not be charged for taking part in the investigation.

• Recruitment materials may state that subjects will be paid, but should not emphasize the payment or the amount to be paid, by such means as larger or bold type.

Initial contact with participants

The first contact prospective study subjects make is often communication with a research team member to determine basic eligibility for the specific study. The IRB may ask to review full scripts for recruitment and screening conversations, particularly when the person conducting the discussions is relatively inexperienced in research (research assistants, community partners, etc.), or when studies involve sensitive topics or vulnerable populations. The IRB must assure the procedures followed adequately protect the rights and welfare of the prospective subjects. In some cases, personal and sensitive information is gathered about the individual. The study submission should describe how this initial information will be handled.

• What happens to information collected from individuals who are ineligible? Is it kept, or destroyed? If kept, how long and where?

• Are paper copies of records shredded or are readable copies put out as trash?

• Are any other protections used to ensure the confidentiality of data collected at this stage? The acceptability of the procedures depends on the sensitivity of the data being gathered

FDA Information Sheet: Recruiting Study Subjects

UWM IRB SOP 402: Informed Consent (PDF)

FDA: Food and Drug Administration

IO: Institutional Official – individual who is legally authorized to act for the institution and ensures the effective functioning of the IRB

IRB: Institutional Review Board

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually

PI: Principal Investigator

UWM: University of Wisconsin – Milwaukee

The initial approval of research is based on both the PI’s presentation of information and the IRB’s assessment of the risks, benefits, and anticipated results of the research as set forth in the protocol application. At the time of initial review, the IRB determines a period of approval and the frequency of any continuing review based on the type and degree of anticipated risk for subjects and/or others. Depending on the degree of risk, the IRB may conduct continuing review at a fully convened meeting, may conduct continuing review under expedited review procedures, or may not require continuing review. If continuing review is not required, the PI will need to report whether the study is active or closed on a routine basis (every year for studies eligible for expedited review and every three years for studies that qualify for an exemption). The IRB may approve the research for a period less than one year when deemed necessary. Examples of studies that might receive a shorter review period would be if there are concerns regarding the risks of the study, the PI’s level of experience or competency to conduct the research, or a history of non-compliance with IRB-approved protocols or institutional policies and procedures. If the IRB believes or finds that an investigator has not conducted the research according to the IRB approved protocol, the IRB may require verification from sources other than the investigator that no material changes in the conduct of the research have occurred since previous IRB review and approval (e.g., auditing or monitoring of consent documentation). This verification should be in writing and submitted for IRB review along with the Continuing Review Form. Any requirement of verification will be communicated to the PI by the IRB in writing. The IRB conducts continuing review of research covered by this policy at intervals appropriate to the degree of risk. This means that continuing review will occur on or before the end of the approval period. If continuing review is not required, the IRB will still require periodic updates, in writing, regarding the study status from the PI. If the PI does not submit a study status update prior to the established date, the IRB will close the study.

Required Content for a Continuing Review:

1. The most current IRB approved protocol, informed consent document, and recruitment material.

2. A continuing review form that includes:

• a. A summary of the progress of the research at UWM and other sites, if appropriate.
• b. A summary of any preliminary results or findings from this research at UWM and other sites.
• c. A summary of any recent literature, findings, or other relevant information that might affect the risks associated with the research, the risk-benefit analysis, or a subject’s willingness to continue participation.
• d. The total number of subjects accrued since the initial approval or the last continuing review and the total number of subjects enrolled to date.
• e. A summary of recruitment and informed consent process information and mention of any problems.
• f. A summary of any unanticipated Adverse Events that have occurred since the initial review or the most recent continuing review, including whether they were of unanticipated frequency and/or severity, related to the research intervention itself, procedure, drug, device or biologic, and whether they modify the risk-benefit analysis, result in modifications to the research protocol to further minimize risk, and/or to the informed consent document.
• g. A description of any amendments to the research protocol or informed consent documents that have been reviewed and approved by the IRB since the most recent initial or continuing review approval.
• h. Any proposed amendments to the research protocol or informed consent documents

Continuing Review Determinations

1. The IRB makes the following determinations to approve research for continuation:

• a. That the research continues to satisfy the criteria set forth in 45 CFR § 46.111 regarding minimizing risks, the anticipated risks remain reasonable in light of the potential for benefit, and there is a plan for an equitable selection of subjects, an adequate informed consent process and documents, provisions for monitoring the data for safety, and provisions to ensure the privacy of subjects and confidentiality of data collected.
• b. Where applicable, the additional protections for vulnerable subjects such as pregnant women, fetuses, prisoners, and children as specified by regulations and the IRB, are in place and remain adequate.
• c. That the informed consent documents are accurate and complete, and any significant new findings that may affect a subject’s willingness to continue participation have been incorporated into the documents and communicated to research subjects in active treatment, if the IRB determines such information might affect their willingness to continue in the research.
• d. Whether the research requires verification from sources other than the PI (e.g., other institutional review boards, the FDA, Sponsors, or institutional sources or committees) that no material changes in the research have occurred since the previous review. The IRB may request an audit of study files to ensure adequate protections if there are concerns that there may have been material changes without prospective IRB review and approval.

Continuing Review by the Convened IRB

1. An online continuing review form must be submitted on or before the IRB meeting submission deadline for full committee review.

2. For research that was initially approved by the full board IRB as more than minimal risk, continuing review will also be conducted by the full board IRB using the same procedures used during initial review.

3. The IRB may make the following decisions:

• a. Approved: Approve as submitted.
• b. Approved with Conditions: Conditional fulfillment is required to secure approval. The PI’s response may be reviewed through expedited procedures.
• c. Tabled: Table the discussion of the research because additional information and/or protocol revisions are required.
• d. Disapproved: The research protocol cannot be approved as proposed.

4. The decisions will be based on the votes of a simple majority (more than 50%) of the voting members present at a full board IRB meeting.

5. The IRB office staff communicates the determinations of the IRB, in writing via email, to the PI and co-investigators, if applicable.

6. Meeting minutes are sent to the IO monthly and made available to others within the institution upon request, so all can be aware of the IRB actions.

Review by Expedited Procedures

1. For research protocols the IRB initially approved under expedited procedures or determined by the full board IRB to be minimal risk, the IRB conducts continuing review under expedited procedures. If new risks or information have been identified by the PI or IRB reviewer, full board review could be warranted.

2. Research protocols previously approved by the full IRB may be eligible for review under expedited review procedures in accordance with 45 CFR § 46.110, under either Category 8 or 9:

a. Category

8: Continuing review of research previously approved by the full board IRB as follows:

• a. Where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow up of subjects; or ii. Where no subjects have been enrolled and no additional risks have been identified; or iii. Where the remaining research activities are limited to data analysis.
• b. Category 9: Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where Categories 2 through 8 do not apply but the IRB has determined and documented at a full board meeting that the research involves no greater than minimal risk and no additional risks have been identified.

3. The IRB is informed of all continuing reviews approved under expedited review procedures on the next available meeting agenda and this is documented in the IRB meeting minutes in accordance with 45 CFR § 46.110(c) and 21 CFR § 56.110(c). Meeting minutes are sent to the IO monthly and made available to others within the institution upon request.

Study Status Update (continuing review not required)

1. The following IRB approved protocols do not require continuing reviews.

• a. Studies that qualify as exempt research under 45 CFR 46.104
• b. Studies approved after January 21, 2019 under expedited review procedures (unless the study must also comply with FDA regulations or the IRB determines and justifies that continuing review is required and communicates this to the PI)
• c. Studies approved after January 21, 2019 by the convened/full IRB and have progressed to the following activities:

1. I. The study is not required to apply FDA human subjects research regulations, and
2. ii. Data analysis, including identifiable private information or identifiable bio-specimens, or
3. iii. Accessing follow-up clinical data from procedures that subjects would undergo as part of their clinical care.

2. The UWM IRB will require study status updates as described below:

a. Exempt Research

• I. Expiration dates will be three years after initial approval and three years after each notification to the IRB that the study is still active.
• ii. The PI must report the current study status, i.e. whether the study is still active or can be closed.
• iii. If no study status is submitted to the IRB by the expiration date, the IRB will close the study and the PI will receive an email notification of the close out.   

b. Expedited Review Research or Research approved by a convened IRB that is in data analysis or follow-up clinical data stages. Research must have an initial approval date on or after January 21, 2019.

• I. Expiration dates will be one year after initial approval and one year after each notification to the IRB that the study is still active.
• ii. The PI must provide the following information to the IRB

1. Status, i.e. whether the study is still active or can be closed.

2. Any changes to funding status.

3. Whether there have been any changes to the approved study materials, and the date of IRB amendment approval.

4. Any changes to the study risks or whether any protocol deviations, problems or unexpected events related to the study have occurred.

• iii. If no study status is submitted to the IRB by the expiration date, the IRB will close the study and the PI will receive an email notification of the close out.

Expiration Dates

After the initial approval period, the IRB may use one of two methods for determining the expiration date for subsequent continuing reviews:

1. The expiration date is calculated based on the date that the IRB office staff determine any conditions are met and issue the continuing review approval letter. Example: A study is initially approved for 12 months on May 2, 2019 and expires May 1, 2020. IRB office staff issue the approval letter on April 30, 2020. The new expiration date will be April 29, 2021.

2. If a review is completed within 30 days of the expiration date, the original expiration date may be retained and carried from year to year. Example: A study is initially approved for 12 months on May 1, 2020 by the full board. The study expires April 30, 2021, but the closest full board review date is April 2, 2021. If the board approves the continuing review on April 2, 2021, IRB office staff may elect to retain the April 30 expiration date. The new approval period would be May 1, 2021 – April 30, 2022.

Study Completions and Close Outs

1. IRB approved studies may be closed in the following circumstances:

• a. All study activities, including data analysis, are complete
• b. Study activities are limited to the analysis of de-identified data and/or report writing. There is no possible way for anyone to link data to individual subjects and any key linking study IDs to subject identifiers has also been destroyed.

2. Studies requiring Continuing Reviews.

• a. If a study meets the criteria for closure listed above, the PI must complete and submit the Continuing Review Form to the IRB.
• b. Once submitted, the IRB will acknowledge the completion/closing of the study and terminate IRB approval.
• c. If a continuing Review Form is not received by the IRB prior to the study expiration date, the study will be closed by the IRB and a close out notification will be sent, via email, to the PI.

3. Studies not requiring continuing reviews

• a. If the PI notifies the IRB that the study is complete, the IRB office staff will maintain a record of the update in the study file and terminate IRB approval.
• b. If no study status is submitted to the IRB by the expiration date, the IRB will terminate the study and the PI will receive an email notification of the close out.

45 CFR § 46 (Common Rule) 21 CFR § 56 (FDA)

OHRP Continuing Review Guidance (2010)

UWM IRB SOP 404: Continuing Review & Study Closure (PDF)

Full board meeting: A convened meeting of the IRB at which a quorum of members is present

Full board studies: Research studies that require review by the convened IRB

IO: Institutional Official; individual who is legally authorized to act for the institution and ensures the effective functioning of the IRB

IRB: Institutional Review Board

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually

PI: Principal Investigator

The Principal Investigator must conduct the research in accordance with the specific methods described in the application that was approved by the IRB. If a PI wishes to make changes to a previously approved research project, these changes must first be submitted to and approved by the IRB. No changes in approved research may be initiated without IRB review and approval, except when necessary to eliminate apparent immediate hazards to research subjects. The IRB reviews amendments to previously approved research in accordance with:

1. the level of risk of the study as a whole, and

2. the level of risk of the proposed changes. Amendments may be reviewed at a full board meeting or via expedited procedures.

When determining the appropriate review level for an amendment, IRB office staff consider which of the “three P’s” are affected by the changes:

1. Purpose

2. Population under study

3. Procedures Most amendments that impact only one of these and do not involve an increase in risk to participants are considered minor amendments. These are generally reviewed by IRB office staff. Amendments that affect two or more of the “three P’s”, or where the risk to participants is increased (including risks related to procedures and methods, and modifications that might negatively impact the statistical analysis of the research), are treated based on the level of review of the initial study. (Note: in most cases, amendments affecting all 3 P’s are usually significant enough to be considered a different study entirely, and the IRB recommends that these be submitted as a new study rather than an amendment.)

• Exempt studies: Amendments are reviewed by IRB office staff only, unless the changes are significant enough that the study no longer qualifies for exempt status. In this case, the amendment would receive either expedited or full board review, in accordance with the level of risk of the changes.

• Expedited studies: Amendments receive expedited review, unless the changes raise the study to the level of more than minimal risk and full board review is required. Expedited reviews may be conducted by the IRB office staff only, or one or more additional reviewers may be assigned.

• Full board studies: Minor changes may receive expedited review by IRB office staff and/or one or more reviewers. Significant changes must receive full board review. IRB office staff, primary reviewer(s), and/or the Chair determine whether a change is “minor” vs. “significant”. If there is not consensus, the amendment is sent to the full board.

Expedited Review Process

Applies to amendments for most exempt and expedited studies, and for minor changes to full board studies.

1. The researcher submits an amendment through the electronic submission system. All documents affected by the amendment must be included. Changes should be marked in the documents so the IRB office staff and reviewer(s), if applicable, can clearly see what is different from the currently approved version.

2. IRB office staff conducts an initial review and determine the level of review required. IRB office staff may act as the sole reviewer if they feel they have adequate expertise to complete the review without input from additional reviewers, or may assign additional reviewer(s).

3. The IRB office staff and any additional reviewer(s) complete the appropriate review checklist and recommend one of the following actions:

• a. Approve as submitted
• b. Request revisions
• c. Assign an additional IRB member to review
• d. Refer to the convened IRB for review Note: Amendments may not be disapproved using expedited procedures. If the reviewer(s) recommend disapproval, the amendment must be referred to the full board.

4. The IRB office staff communicates any request for revisions to the researcher in writing.

5. Upon resolution of any requested changes, the IRB office staff issues the approval letter

6. The approval of an amendment does not change the original approval period or the expiration date of the study.

7. IRB office staff includes a list of all expedited actions on the next available meeting agenda and documents the IRB’s approval of these actions in the IRB meeting minutes. Agendas and minutes are made available to all IRB members and the IO regularly, and to anyone else in the institution upon request. An IRB member may request that any amendment given expedited approval be brought before the convened IRB for review.

Full Board Review Process Applies to full board studies where the changes are not minor, or to exempt/expedited studies if the changes involve more than minimal risk.

1. The researcher submits an amendment through the electronic submission system. All documents affected by the amendment must be included. Changes should be marked in the documents so the IRB office staff and reviewer(s), if applicable, can clearly see what is different from the currently approved version.

2. IRB office staff conducts an initial review and completes the reviewer checklist. One or more additional reviewers may be assigned.

3. The amendment is placed on the next available meeting agenda and the PI and/or SPI are invited to the meeting.

4. The convened IRB reviews the amendment and may take one of the following actions, based on the votes of the majority (more than 50%) of the voting members present at a full board meeting.

• a. Approve as submitted
• b. Request revisions
• c. Table, pending additional information
• d. Disapprove

5. The date of approval of an amendment does not change the original approval period or the expiration date of the study, unless the IRB determines that the changes warrant reviewing the study more frequently (example: a 6 month approval period rather than the usual 12 months). In that case, a new expiration date may be issued.

6. The IRB office staff communicates any request for revisions to the researcher in writing.

7. Once any requested changes have been made, the IRB office staff issues the approval letter.

8. The amendment, discussion of any controverted issues, and actions taken by the IRB are documented in the meeting minutes.

45 CFR § 46.110 21

CFR § 56.110

UWM IRB SOP 405: Amendments of Approved Studies (PDF)

IRB: Institutional Review Board

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually

OHRP: Office of Human Research Protections; a division of the federal Health and Human Services department (HHS) that oversees human subjects research

Pre-2018 regulations: Regulations governing all research that was approved prior to January 21, 2019. The regulation changes were originally slated to go into effect January 2018 (hence “pre-2018”), but the implementation was delayed for a year.

UWM: University of Wisconsin – Milwaukee

In 2017 OHRP issued new federal regulations governing human subjects research, which went into effect on January 21, 2019. Under the regulations, institutions were allowed to decide whether studies approved before the effective date would continue to be reviewed and administered under the previous version of the federal regulations or be transitioned to the new regulations. At UWM, previously approved studies continue to be governed by the pre-2018 regulations, and only new studies that receive initial approval on or after January 21, 2019 follow the 2018 regulations.

At UWM, studies reviewed and approved under the pre-2018 regulations differ from newer studies in the following areas:

• Continuing review requirements
• Exempt categories
• Required elements of informed consent
• Clinical trials SOPs governing those areas apply to new (2019 onwards) studies only, and the processes governing older studies are outlined in this document. Any process not outlined here is identical to the process followed by all new studies, and the appropriate SOP for that process should be referenced for details.

Continuing Reviews All expedited and full board studies are required to undergo a continuing review not less than annually. Continuing reviews are submitted to the IRB in advance of the study expiration date. IRB office staff perform the review and may assign the continuing review to a reviewer for expedited review or send to the full board, depending on the level of risk.

Exempt Review Categories The exempt categories under the pre-2018 regulations are as follows:

(1) Research, conducted in established or commonly accepted educational settings, involving normal educational practices such as research on regular and special education instructional strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

(2) Research that involving the use of interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior if at least one of the following criteria is met:

• (I) The information obtained is recorded by the investigator in such a manner that human subjects cannot be identified, directly or through identifiers linked to the subjects;
• (ii) Any disclosure of the human subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, or reputation.

(3) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if: (I) the human subjects are elected or appointed public officials or candidates for public office; or (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

(4) Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.

(5) Research and demonstration projects that are conducted or supported by a Federal department or agency, or otherwise subject to the approval of department or agency heads that are designed to study, evaluate, improve, or otherwise examine public benefit or service programs, including procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs.

(6) Taste and food quality evaluation and consumer acceptance studies:

• (I) If wholesome foods without additives are consumed, or
• (ii) If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

Required Elements of Informed Consent Basic elements:

• Statement that the study involves research and an explanation of the purposes of the research
• The expected duration of the subject’s participation
• Description of the procedures to be followed and identification of any procedures which are experimental
• Description of any reasonably foreseeable risks or discomforts to the subject
• Description of any benefits to the subject or to others which may reasonably be expected
• Disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject
• Statement describing the extent to which confidentiality of records identifying the subject will be maintained
• For research involving more than minimal risk, an explanation as to whether any compensation and any medical treatments are available if injury occurs, and if so, what they consist of, or where further information may be obtained
• Research, Rights or Injury: An explanation of whom to contact for answers to questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury
• Statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled

Additional elements, as appropriate:

• Statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant), which are currently unforeseeable
• Anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject’s consent
• Any additional costs to the subject that may result from participation in the research • The consequences of a subject’s decision to withdraw from the research and procedures for orderly termination of participation by the subject
• Statement that significant new findings developed during the course of the research, which may relate to the subject’s willingness to continue participation, will be provided to the subject
• The approximate number of subjects involved in the study Clinical Trials New regulations require that the consent form for federally funded clinical trials be posted to a website that is publicly accessible. This is not required in the pre-2018 regulations.

45 CFR 46 (pre-2018) SOP 401 Review of Research

SOP Appendix 401.1 Exempt Review Categories

SOP 402 Informed Consent

SOP 404 Continuing Review & Study Closure

UWM IRB SOP 406: Studies Initially Approved Before January 2019 (PDF)

Full board review: A review conducted at a convened meeting of the IRB at which a quorum of members is present

IO: Institutional Official; the individual who is legally authorized to act for the institution and ensures the effective functioning of the IRB

IRB: Institutional Review Board

IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually

PI: Principal Investigator

Unanticipated Problems: Any problem occurring during the course of a research study that was not considered when the study was originally reviewed by the IRB.

UPIRSO: Unanticipated Problem Involving Risk to Subjects or Others

The IRB is responsible for monitoring the safety and welfare of human subjects. Part of this monitoring is ongoing review and assessment of Unanticipated Problems related to participation in the research. These may include adverse events, unexpected occurrences with the potential for harm, or subject complaints. (Protocol deviations and other types of noncompliance are treated separately in SOP 502: Noncompliance.)

Unanticipated Problems Involving Risks to Subjects or Others

Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) are any occurrences during the conduct of a research study that result in harm, or that could result in harm if immediate action were not taken. The person harmed may be either a subject or others, i.e., someone else tangentially related to the research, such as research personnel or other individuals not directly part of the research. Specifically, an Unanticipated Problem is considered a UPIRSO if it meets all of the following criteria:

• 1. The event is unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
• 2. The event is related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); AND
• 3. The occurrence suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Only Unanticipated Problems related to the research or possibly related to research must be reported. Related Unanticipated Problems occur as a result of

• The interventions and interactions used in the research; or
•  The collection of identifiable private information in the research.
• Unanticipated Problems are not considered related and do not need to be reported to the IRB if they are the result of:
• An underlying disease, disorder, or condition of the subject; or
• Other circumstances unrelated to the research or any underlying disease, disorder, or condition of the subject.
• The Principal Investigator must monitor and document the unanticipated problems related to the research throughout the life of the study. The PI must also evaluate whether the unanticipated problems are related to the research and what corrective actions should be implemented, if any, to prevent a similar occurrence in the future. If the reporting threshold is met, the PI must report the unanticipated problems to the IRB and implement corrective actions. The PI is encouraged to consult with the IRB for questions or concerns related to unanticipated problems, or for assistance in determining whether the reporting threshold is met.

Study-Related Complaints

Unanticipated Problems may also take the form of complaints. While complaints typically are made by a research subject, they can originate with anyone who is aware of the research. Complaints may be made to the research team or directly to the IRB. Depending on the exact nature of the complaint, they may require immediate reporting to the IRB, or may be reported at the time of continuing
review. The PI is encouraged to consult with the IRB at any point for questions or concerns related to subject complaints, or for assistance in determining whether the reporting threshold is met.

Reporting
Subject deaths must be reported to the IRB within 24 hours. Otherwise, UPIRSOs must be reported to the IRB within 10 business days. The initial notification should be by phone or email to the IRB office, followed by the submission of a Reportable Event. Unanticipated Problems that are not UPIRSOs must be reported within 10 business days via Reportable Event when, regardless of severity, the problem may alter the IRB’s analysis of the study’s risk to benefit ratio or where substantive changes in the research protocol or informed consent may be needed. Separate notification to the IRB office by phone or email is advised.

Examples:

Inclusion or exclusion criteria must be modified to mitigate a newly identified risk; New monitoring procedures need to be implemented to ensure subject safety;
Study enrollment is halted due to the Unanticipated Problem;
Newly identified risks require notification to existing subjects and/or a modification to the informed consent.

All Unanticipated problems, both those that met immediate reporting requirements outlined above and any others that have been encountered, must be included in the annual Continuing Review or update summary to the IRB. If no Unanticipated Problems have occurred since the previous review, the researcher should state this.

Review Process
IRB office staff receive notification of an Unanticipated Problem and review the report to determine:

• 1. The effect of the Unanticipated Problem on the risk-benefit relationship of the research, (i.e., no change in risks or benefits; increased risks with no change in benefits; or increased risk and decreased benefits).
• 2. Whether the research protocol requires modifications.
• 3. Whether the informed consent process and/or informed consent document requires modification to inform currently enrolled subjects or subjects who have completed their research participation.
• 4. Whether frequency of continuing review should be increased.
• 5. Whether additional safeguards should be implemented to minimize risk and/or maximize the potential for benefit. Depending on the nature and severity of the Unanticipated Problem, the IRB Office staff may consult with additional IRB members, the Chair, and/or the IO as needed, and may refer the Unanticipated Problem to the convened IRB. The IRB office staff, Chair, and/or the IO may request that the Principal Investigator suspend research activities during the review process. However, only the Full Board may terminate the research.

Full Board IRB Review of an Unanticipated Problem When an Unanticipated Problem is referred to the Full Board for review, it may be reviewed at the next regularly scheduled meeting or, if the matter requires special urgency, a special ad hoc meeting may be called. The convened IRB may, at its discretion, implement any of the following actions:

•  Acknowledge that the risk-benefit relationship has not changed and continue monitoring at the current continuing review interval.
• Request further information from the Principal Investigator.
•  Require modifications to the research protocol and/or informed consent document.
• Require notification to currently enrolled subjects so they may decide whether they wish to continue participation.
• Require notification of subjects who have completed their participation in the  research.
• Shorten the period of IRB approval (decreasing the time interval for continuing review reporting and IRB review).
• Implement additional safeguards (i.e., more frequent specific monitoring).
• Suspend enrollment of new subjects.
• Refer for further review as potential non-compliance.
• Terminate the research.
• Other actions deemed appropriate by the IRB. These actions must, however, be related to the research protocol(s) being evaluated. Actions related to researchers’ employment or status are governed by University policies and are not in the IRB’s purview. The IRB office staff will notify the Principal Investigator in writing of the IRB’s determination. If the IRB determines that research activities should be suspended or terminated, IRB office staff will notify the IO. If appropriate, the IRB office staff or IO will notify the Sponsor, pertinent federal compliance offices, and internal University Administrators.

Subject Complaints

• If the IRB receives a complaint, IRB office staff will notify the PI that a complaint has occurred and provide relevant details, while keeping the identity of the individual making the complaint confidential. In some cases, it may be appropriate to reveal the identity of the complainant (e.g., if the complaint is related to subject payment, the identity may need to be revealed in order to issue compensation). This is done at the discretion of IRB office staff.
• If the PI receives a complaint that can be easily resolved, the appropriate action should be taken, an amendment submitted to the IRB if necessary, and the complaint reported at the next continuing review or annual update.
• If the PI receives a complaint that cannot be easily resolved or that involve a serious issue, this should be reported to the IRB as a Reportable Event within 10 business days. When in doubt, the PI may consult with IRB office staff to determine whether the complaint requires immediate reporting.
  For all complaints:
• 1. IRB office staff will review the complaint and request additional information from the complainant and PI as needed.
• 2. IRB office staff work with the PI to determine the best way to resolve the issue, consulting with the Chair, other IRB members, and/or the IO as needed.
• 3. The PI may be required to submit an amendment if any study procedures or documents need to be modified as a result of the complaint.
• 4. For serious complaints, IRB office staff will notify the Chair and IO within 1 business day of receiving notification of the complaint. “Serious” is defined as a complaint that:

Indicates serious noncompliance on the part of the investigator;
Involves allegations of misconduct or illegal activity on the part of the investigator;

• Indicates that the risk-benefit ratio of the research may need to be re-assessed; or
• Requires prompt action by the IRB to resolve the complaint or mitigate potential harm.

45 CFR § 46.103(b)(5)
21 CFR § 56.108(b)(1)
Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events: OHRP Guidance (2007) https://www.hhs.gov/ohrp/regulations-andpolicy/guidance/reviewing-unanticipated-problems/index.html
SOP 502 Noncompliance

Allegation of Noncompliance: An assertion of noncompliance that has not yet been investigated to determine whether it is true or false.
CFR: Code of Federal Regulations
Finding of Noncompliance: When an investigation into an allegation has determined the allegation to be true. Full board meeting: A convened meeting of the IRB at which a quorum of members is present IO: Institutional Official; individual who is legally authorized to act for the institution and ensures the effective functioning of the IRB

IRB: Institutional Review Board
IRB office staff: the IRB Manager, IRB Administrator, and any other IRB office staff, either collectively or individually
Noncompliance: Any deviation from University of Wisconsin-Milwaukee IRB policies and procedures, federal regulations, or state law
UWM: University of Wisconsin – Milwaukee

IRB, and in accordance with all applicable federal and state laws, University of Wisconsin System policies, and UWM policies and procedures.
Noncompliance is failure to follow the laws, university policies, or IRB SOPs governing human subjects research. Similarly, deviations from the approved research plan are also noncompliance, except when necessary to eliminate an apparent immediate hazard to research subjects. There are three categories of noncompliance: Serious, Continuing, and General.

• Serious Noncompliance: All noncompliance that substantially affects participants’ rights and / or welfare, or that impacts the risks or benefits of the research.
• Continuing Noncompliance: A pattern of noncompliance that indicates an inability or unwillingness to comply with the regulations or the requirements of the IRB.
• General Noncompliance: Noncompliance that is neither serious nor continuing.
  General noncompliance may be reviewed by IRB office staff, in consultation with the IRB Chair, other IRB members, and the IO as needed.

Allegations of Serious or Continuing Noncompliance will be investigated by an IRB Noncompliance Subcommittee, who may resolve the investigation or refer the allegation of noncompliance to the Full Board.
Any actions taken by the IRB are limited to those directly related to human subjects research, such as requiring changes to the protocol, modifying the approval period, or suspending the research. Disciplinary actions related to researchers’ employment or status will be governed by University policies and are not in the IRB’s purview.
All findings of noncompliance that the IRB determines to be serious or continuing noncompliance will be promptly reported to the IO, who will then report the incident to the appropriate internal and external entities.

All reports and complaints of noncompliance should be directed to the IRB office staff. The IRB office staff will investigate all allegations of noncompliance.
Minor protocol deviations and their corrective actions may be reviewed by IRB office staff alone. These are deviations that are easily resolved and do not affect the regulatory criteria for approval. Other types of noncompliance will be sent to one or more IRB members for review. The reviewers may:

• Recommend corrective actions
• Request further review by additional members or the convened IRB.
  Notifications of all noncompliance reviews will be included in IRB meeting agendas and minutes.

Noncompliance Subcommittee Review

Allegations or findings of noncompliance will be referred to an IRB Noncompliance Subcommittee for evaluation in the following cases:

• All allegations of serious or continuing noncompliance will be investigated by a
  subcommittee, regardless of source.
• The researcher disputes that noncompliance has occurred
• The assigned reviewer of a noncompliance has requested further review by additional members or by the convened IRB.

This subcommittee will be composed of two or more members of the IRB, including (or in addition to) one IRB office staff member. The members of the subcommittee will

1. Review the nature of the noncompliance• Complete a reviewer form/checklist to document their findings.
2. If the subcommittee members unanimously agree that the non-compliance is not serious or continuing, the subcommittee may make a determination and recommend corrective actions. Notifications of this type of noncompliance review will be included in the IRB meeting agendas and minutes.

For serious or continuing noncompliance, or any other noncompliance where the
subcommittee determines that the convened IRB should review the noncompliance, the subcommittee will provide a written statement to the IRB for consideration and vote. The statement will include the following:

1. Whether the subcommittee believes the allegation is true or false.
2. Whether the subcommittee believes the noncompliance is general, serious, or
   continuing.
3. Any recommended actions for the IRB to take.

Convened IRB Review
The IRB will review the recommendation of the IRB noncompliance subcommittee at a full board meeting. All IRB members will be provided with a copy of the approved protocol, all relevant IRB files and documents, and the report of the IRB noncompliance subcommittee. A member of the IRB noncompliance subcommittee will serve as a primary reviewer. The IRB may accept or reject the subcommittee’s recommendations. If the IRB rejects the subcommittee’s recommendations, then the IRB may modify the recommendations or propose other actions.
The IRB will assess and vote, within two meetings, upon:

• Whether any allegations of noncompliance were true
• Whether any findings of noncompliance were general, serious, or continuing
• What corrective actions, if any, should be taken. If necessary, the IRB may request additional information before issuing determinations. The IRB may request any appropriate additional consultation and expertise to resolve noncompliance.
• Corrective Actions Potential IRB actions are limited to the following:
• Requiring modification to the research protocol;
• Requiring modification to the consent process;
• Requiring researchers to contact past or current participants with additional information and providing them the opportunity to withdraw from participating or withdraw their data, if applicable;
• Requiring researchers to re-consent participants;
• Modifying the approval period;
• Suspending the research (may be either a specific protocol or multiple research studies conducted by the researcher); or
• Terminating IRB approval of the research.

Termination requires action by the convened IRB. If an individual reviewer or
subcommittee feels that termination is warranted, the noncompliance must be sent
to the convened IRB for review.

Temporary Suspension of Research
If the IRB, IRB Chair, and/or IO determines that the immediate suspension of some or all research activities is necessary while the noncompliance is reviewed, the IRB office staff will send the researcher a written notice detailing the specific activities to be halted and a rationale. The IRB Chair and the IO will be copied on all such notifications.

Institutional Official Responsibilities
The IO receives written notice of all noncompliance via the IRB meeting agendas and minutes. The IO has the discretion to request additional review of any instance of noncompliance. In the event of Serious or Continuing Noncompliance, IRB office staff or the IRB Chair will notify the IO. The IO will notify, as applicable:

• The study sponsor
• Appropriate federal agencies (e.g., Office of Human Research Protections, Food and Drug Administration, etc.)
• Appropriate university administrators
• The Office of Research
• The researcher’s department chair and dean

45 CFR 46.113