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WSU Guidelines Manual: Human Subjects in Research

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Introduction

This Weber State University (University) Institutional Review Board (IRB) Procedure Manual (“Written Procedures”) complies with the requirements to have written procedures in 45 Code of Federal Regulations (CFR) § 46.108(a)(3-4) and 21 CFR § 56.108(a-b). The University has registered the IRB with the United States (US) Department of Human Health Services (HHS). The IRB has the organization number of IORG0003630 and the Federal Wide Assurance (FWA) number of FWA00022946 (see FWA Lookup).

Title 45 CFR Part 46 Subpart A supplemented by Subparts B, C and D (Common Rule ) (see 45 CFR Part 46) and its corollary regulations for the United States Food and Drug Administration (FDA) (see e.g. 21 CFR Parts 50, 56, 312, and 812) regulate human research. The Office for Human Research Protections (OHRP), which is an office in the HHS, enforces the Common Rule (see OHRP Webpage). Although the FDA is an agency within HHS, research conducted under FDA’s purvey, as noted above, is subject to different regulations from other HHS divisions (see FDA Webpage). Other divisions under HHS such as the National Institute of Health (NIH) are subject to the Common Rule.

On January 19, 2017, drafting agencies revised and modernized the Common Rule (Revised Common Rule) and published it in the Federal Register (see Federal Register). The Revised Common Rule will come in effect on January 21, 2019 except for the cooperation research (see 46 CFR § 45.114(b)) which will come into effect on January 20, 2020 (see Federal Register). Once approved, the parts of the Written Procedures that comply with the current version of the Common Rule will come into effect immediately once approved. The parts that do not comply with the current version of the Common Rule will apply once the Revised Common Rule comes into effect.

The Written Procedures adopts the sequencing, general section headings, and subsection headings found in “Guidance for Institutional Review Boards (IRBs) IRB Written Procedures: Draft Guidance” which HHS released as a draft in August 2016 (see Guidance for IRB Written Procedures). While this guidance was only published for comment purposes and provides non-binding recommendations, this adoption of the HHS guidance aligns the Written Procedures with the HHS’s most current thinking on how to sufficiently comply with the written procedures requirements in CFR § 46.108(a)(3-4) and 21 CFR § 56.108(a-b). This will ensure that the University has adequate procedures to protect human research participations. Additionally, the adoption of this HHS guidance will ensure the compliance with the law and facilitate internal and external audits. Because the Written Procedures substantively follow this HHS guidance, there are sections in the Written Procedures that are redundant. This redundancy will enable researchers and auditors to quickly review relevant sections of the Written Procedures to learn pertinent University procedures without having to review its entirety.

Following the formatting of the “Guidance for Institutional Review Boards (IRBs) IRB Written Procedures,” the chapters have chapter headings with capitalized Roman numerals (e.g. I, II, etc.). Each chapter starts on a new page. In Chapter V, the subchapters divide each chapter with subchapter headings that have capitalized Latin letters (e.g. A, B, C etc.). The parts divide each chapter and subchapter with part headings that have Hindu-Arabic numerals (e.g. 1, 2, etc.). The Hindu-Arabic numerals, in the part headings, continue to ascend and do not restart when transitioning between chapters (e.g. the first part in the Chapter II. starts with the Hindu-Arabic numeral 26 and does not restart to 1). Sections divide each part with section headings that have Hindu-Arabic numerals followed by a period and subsequent Hindu-Arabic numerals (e.g. 2.1, 2.2, etc.). The first Hindu-Arabic numeral in each section heading corresponds with the Hindu-Arabic numeral in the part heading.

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Section I. Conducting Initial and Continuing Review of Research and Reporting IRB Findings and Actions to the Investigator and the Institution (see e.g. 45 CFR § 46.108(a)(3)(i); see also 21 CFR § 56.108(a)(1))

1. The institution’s process for determining whether a study is subject to review by the IRB

To determine whether a study is subject to review by the IRB, the Principal Investigator (PI) and IRB reviewer must consider the following questions:

  1. Does the FDA regulations or Common Rule potentially apply?
  2. Does the activity constitute research (for non-FDA HHS supported research) or a clinical investigation (for FDA regulated studies)?
  3. Does the activity involve human subjects?
  4. Is the PI engaged in human subject’s research?
  5. If the PI is not engaged in human subject’s research, is the PI engaged in quality improvement or program evaluation activities?

1.1 Applicability of FDA or Common Rule

To determine whether the FDA regulations or the Common Rule apply, the PI and IRB reviewer should consider the following questions:

  1. What is the funding source?
  2. Are there FDA regulated devices, drugs or biologics involved in the activity? and
  3. Will the PI consider the US market for devices, drugs or biologics?

If the funding source is from HHS, then the Common Rule applies. If the activity involves devices, drugs, or biologics, the FDA regulations apply. If the PI is thinking of commercializing the devices, drugs, or biologics in the US market, then the FDA regulations apply. The PI is initially responsible for making the determination of whether the FDA or Common Rule apply to his/her activities. As applicable, the IRB reviewer will then be responsible for reviewing the PI’s determinations.

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1.2 Research or Clinical Investigation:

Once the PI determines whether the FDA regulations or the Common Rule apply, then the PI is primarily obligated to determine whether the activity is human research, as regulated by the Common Rule, or a clinical investigation as regulated by the FDA regulations. When there are questions about whether the PI’s activities are non-research/non-clinical investigation activities, the PI is encouraged to do the following:

  1. Consult with his/her peers and IRB members;
  2. Review federal regulations (see 45 CFR Part 6, FDA Regulations);
  3. Review OHRP and FDA interpretation documents and educational materials (see OHRP Education and Outreach, OHRP Policy and Guidance, and FDA Guidance Documents);
  4. Review these Written Procedures; and
  5. Use educational materials such as the Collaborative Institutional Training Initiative (CITI) Program human research modules (see CITI Program Homepage).

The IRB will not require the IRB to review non-research/non-clinical investigation activities.

1.2.1 Research

The PI should make the determination that activities subject to Common Rule are research if they fall within the definition of research found at 45 CFR § 46.102(l). This definition under the Revised Common Rule states:

Research means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program that is considered research for other purposes. For example, some demonstration and service programs may include research activities. For purposes of this part, the following activities are deemed not to be research: (1) Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information, that focus directly on the specific individuals about whom the information is collected. (2) Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters). (3) Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes. (4) Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.

In the Revised Common Rule definition, the drafting agencies removed four categories of activities from the definition of research including:

  1. Scholarly journalistic activities;
  2. Public health surveillance;
  3. Criminal justice activities; and
  4. Authorized operational activities in support of national security missions.

Any PI involved in these activities is not required to receive IRB review.

Other than the removed categories, the definition of research has remained unmodified. This is despite the drafting agencies’ acknowledgment in the Federal Register that critics of definition argue that it is not “sufficiently clear and precise . . . in a way that ma[kes] it immediately obvious which activities f[a]ll under the definition and which d[o] not” (see Federal Register).

Despite the ambiguity in the regulation, OHRP focuses on the terms “systematic investigation” and “generalizable knowledge” to interpret the definition of the term research. OHRP describes systematic investigation to involve a hypothesis and a plan to test the hypothesis. OHRP describes generalizable knowledge to be knowledge applicable to a larger source and generalized to enable additional research. While publication is a way to distribute generalizable knowledge, OHRP notes that publication is not determinative of whether an activity contributes to generalizable knowledge because research may occur which is not published for various reasons.

1.2.1.1 Classroom Activities

Classroom activities may or may not fall within the definition of research under the Revised Common Rule. The University recognizes the need to facilitate classroom research. Accordingly, it has created a system to facilitate the review of exempt research associated with classroom activities. Section 2.2 will outline this exempt review for classroom activities.

The University does not consider classroom activities to be determinative on whether an activity is research. Based on the regulations, the test to determine whether an activity falls within the definition of research involves the following two steps:

  1. Whether the activity is a “systematic investigation”; and
  2. Whether this investigation may contribute to “generalizable knowledge.”

Classroom activities may involve a “systematic investigation” including a hypothesis and a plan to test the hypothesis. Further classroom activities may contribute to “generalizable knowledge” that can be applied to a larger source and generalized to result in additional research. To determine whether the classroom activities are research, it does not matter whether these activities are actually published or distributed outside of a classroom.

1.2.2 Clinical Investigation

The PI should make the determination of whether the activities are clinical investigation as defined by 21 CFR § 50.103 that reads:

Clinical investigation means any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or is not subject to requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that are subject to the provisions of part 58 of this chapter, regarding nonclinical laboratory studies.

 

1.2.3 Quality Improvement and Program Evaluation Activities

Under the Common Rule, research is a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge (see 45 Code of Federal Regulations (C.F.R.) 46.102(l)). Activities which meet this definition constitute research, whether or not they are conducted or supported under a program which is not considered research for other purposes. Many Quality Improvement (QI) and Program Evaluation (PE) activities do not require review by IRB because they do not meet the definition of research (see 82 Fed. Reg. 7149, 7178 to 7179). There is no regulatory definition for QI or PE, but they are often described as being designed to bring about immediate (or nearly immediate) improvements in delivery or system performance. The Office of Human Research Protections (OHRP) indicate that the following QI/PE activities are not human subject research:

  1. Delivering healthcare;
  2. Measuring and reporting provider performance data for clinical, practical or administrative use;
  3. Implementing a practice to improve the quality of patient care;
  4. Collecting patient or provider data regarding the implementation of the practice for clinical, practical, or administrative purposes; and
  5. Analyzing de-identified datasets.

However, OHRP considers QI and PE activities to be research in instances where a project involves an untested clinical intervention and patient outcomes are collected; and these patient outcomes are used to establish evidence of how well the intervention achieves its intended results. OHRP does not consider the intention to publish or not publish QI and PE activities to be determinative on whether these activities are research. (see https://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/quality-improvement-activities/index.html). 
To determine whether QI or PE activities require IRB review, a PI must complete a screening questionnaire so an IRB reviewer may determine whether: 

  1. the QI or PE activities are human subjects research; or
  2. the PI needs to provide more information to make this determination.

The IRB reviewer will indicate to the PI their determination and if the QI or PE activities are determined to be human subjects research, the PI must follow the process in these Written Procedures to receive IRB review for their QI or PE activities.

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2. The institution’s process for determining which HHS-conducted or supported research studies qualify as exempt from the HHS regulations

Section 2.1 discusses exempt research under the Revised Common Rule (see 45 CFR § 46.104). Section 2.2 outlines the process to make exempt determinations for all classroom research activities subject to the Common Rule. Section 2.3 then concludes with a discussion of exempt research under the FDA (see 21 CFR § 56.104).

2.1 Common Rule Exemptions

Exempt research activities fall within the Common Rule’s definition of research. However, exempt research is not subject to the requirements of the Common Rule other than the applicable requirements in 45 CFR § 46.104 (see 45 CFR § 46.104(a)). The University agrees with the OHRP’s recommendations that a PI “not be given the authority to make an independent determination that their research subjects research is exempt.” This is because of the PI’s inherent conflict of interest. Individuals authorized to make exempt determinations should be “well-acquainted with interpretation of the regulations and the exemptions.” Accordingly, the University employs processes that require either of the following:

  1. Knowledgeable reviewers without conflicts of interest make the exempt determinations; or
  2. If developed by the federal government, a decision-making tool makes these determinations.

Until the federal government develops a decision-making tool as outlined below in Section 2.1.1 or unless the research is classroom research as outlined in Section 2.2, designated IRB reviewers will make exempt determinations. The PI will submit to one of the designated IRB reviewers the following documents:

  1. A fully completed application of the use of human subject’s form;
  2. An informed consent statement unless the PI’s justify why an informed consent statement inhibits his/her research;
  3. A certificate of completion of CITI Program training at least within the past three (3) years of the proposed research or a comparable training approved by the IRB Chair; and
  4. Any other supplemental documentation.

After reviewing these documents, the designated reviewer will determine whether the research activities are exempt or not exempt. The designated IRB reviewer will review these submissions in accordance with 45 CFR § 46.104. They will then make written decisions with the rational for their determinations on whether the research activities meet the requirements outlined in 45 CFR § 46.104. The designated IRB reviewer may provide feedback on how the PI can modify his/her submissions to meet these requirements. The designated IRB reviewer will send his/her written decisions to the PI. The designated IRB reviewer will provide the PI with an opportunity to respond in person or in writing. Once the procedure is complete, the designated IRB reviewer will store these submissions and his/her responses in the designated repository.

2.1.1 Decision Making Tool

In the Notice of Proposed Rulemaking (NPRM), the drafting agencies proposed the development of a decision-making tool to make exempt determinations. In the Revised Common Rule, the drafting agencies omitted the decision-making tool from the final regulation. However, the Federal Registry indicates that the federal agencies “will continue to explore development of an exemption decision tool.” If and when this decision-making tool is developed other than the limited review required for 45 CFR § 46.111(a)(7), the decision-making tool will make Common Rule exempt determinations.

If the decision-making tool is developed, the PI is responsible for using the tool to determine whether the proposed research is exempt. The PI is in the best position to input accurately information about the proposed research into the decision tool. Accordingly, the PIs is accountable for the information inputted into the tool to be accurate and complete. Upon using this decision tool, the PI is responsible for submitting to one designated IRB reviewer documentation sufficient to demonstrate that the research was determined to be exempt. This documentation will be stored in the designated repository.

2.1.2 Exempt Categories

The Revised Common Rule establishes the extent to which the exemptions apply to the populations protected in Subparts B, C, and D. So long as the proposed research meets the exempt criteria, all the exemptions apply in Subpart B. Subpart B provides additional protections for pregnant women, human fetuses, and neonates. For Subpart C, which provides additional protections for prisoners, the exemptions generally do not apply. Exemptions may only apply in Subpart C if the PI aims the research at a broader subject population and only incidentally includes prisoners. In the context of Subpart D, which provides additional protections for minors, exemptions d(1), (4), (5), (6), (7) and (8) may apply as the exempt criteria are met. The exemptions in d(2)(i) and (ii) may apply to minors for research involving educational tests or observations of public behavior under two conditions:

  1. The study teams do not participate in these activities; and
  2. The exempt criteria are met (see 45 CFR § 46.104(b)(1-3)).

The Revised Common Rule includes the following categories of research that are exempt from IRB review (see 45 CFR § 46.104(d)):

  1. Instruction, Curricula, and Classroom Management Research (see 45 CFR § 46.104(d)(1))- this research occurs in educational settings that involves the following:
    1. a.  Research on regular or special instructional strategies;
    2. b.  Research not likely to adversely impact:
      1. i.  students’ opportunities to learn or
      2. ii.  impact teachers’ ability to provide instruction or assessment; and
    3. c.  Research on instructional techniques, strategies, curricula, or classroom management methods. Note: This exempt category does not include: test, or survey/interview/observational research, see below.
  2. Adult Survey, Interview and Observational Research (see 45 CFR § 46.104(d)(2))-this research involves subjects who are 18 or older and uses educational tests (cognitive, diagnostic, aptitude or achievement) surveys, interviews, or observations of public behavior; and the research includes one of the following:
    1. a.  Researchers record the information in such a manner that the identity of the subjects cannot be readily ascertained directly or indirectly (pseudonyms/randomized numbers in which characteristics are linked to a particular individual may not be sufficient given study design. For more information, NIST provides an overview on de-identification see NIST);
    2. b.  Disclosures of subjects’ responses would not place subjects at risk of any of the following: civil liability, criminal liability, financial damage, damage to employability, or damage to reputation; or
    3. c.  Researchers employ Weber State University IRB authorized data management procedures in compliance with the guidance from HHS on confidentiality of data as outlined in 45 CFR § 46.111(a)(7)
  3. Minor Observational Research and Educational Tests (see 45 CFR § 46.104(d)(2))– this research is on subjects below the age of 18 involving observations of public behavior or education tests when investigators do not participate in the activities being observed; and the research includes one of the following:
    1. a.  Researchers record the information in such a manner that the identity of the subjects cannot be readily ascertained directly or indirectly (pseudonyms/randomized numbers in which characteristics are linked to a particular individual may not be sufficient given study design. For more information, NIST provides an overview on de-identification see NIST); or
    2. b.  Disclosures of subjects’ responses would not place subjects at risk of any of the following: civil liability, criminal liability, financial damage, damage to employability, or damage to reputation.
  4. Adult Research Involving Benign Behavioral Interventions (see 45 CFR § 46.104(d)(3))– this research is on subjects who are 18 or older that includes:
    1. a.  Research that is brief in duration, painless, harmless, not physically invasive, not likely to have adverse impacts or not likely to be offensive, embarrassing to research subjects, and in instances involving deception, the research subjects are apprised that they may be unware or misled regarding the nature of the research;
    2. b.  Research that includes data collection through verbal or written responses;
    3. c.  Research in which the research subjects prospectively agree to the intervention and data collection; and one of the following:
      1. i.  Researchers record the information in such a manner that the identity of the subjects cannot be readily ascertained directly or indirectly (pseudonyms/randomized numbers in which characteristics are linked to a particular individual may not be sufficient given study design. For more information, NIST provides an overview on de-identification see NIST);
      2. ii.  Disclosures of subjects’ responses would not place subjects at risk of any of the following: civil liability, criminal liability, financial damage, damage to employability, or damage to reputation; or
      3. iii.  Researchers employ Weber State University IRB authorized data management procedures in compliance with the guidance from HHS on confidentiality of data in accordance with 45 CFR 46.111(a)(7).
  5. Research on Existing Data With No Consent Required (see 45 CFR § 46.104(d)(4)) – this is secondary research not requiring consent that involves identifiable private information or identifiable biospecimens that includes at least one of the following:
    1. a.  Publicly available;
    2. b.  Research does not contact subjects or re-identify subjects. Researcher records the information in such a manner that the identity of the subjects cannot be readily ascertained directly or indirectly (pseudonyms/randomized numbers in which characteristics are linked to a particular individual may not be sufficient given study design. For more information, NIST provides an overview on de-identification see NIST);
    3. c.  Research involves identifiable health information regulated by HIPPA for “health care operations” (e.g. improvement activities etc.) or “research” as defined in 45 CFR § 164.501 or “public health activities and purposes” (e.g. disclosure to CDC etc.); or
    4. d.  Research is conducted on behalf of a federal department or agency using government information, which is controlled by the E-Government Act of 2002 and is maintained on systems subject to the Privacy Act of 1974 and, if applicable, the information was gathered subject to the Paperwork Reduction Act of 1995.
  6. Federally Funded Research on Public Benefit Programs (see 45 CFR § 46.104(d)(5))- this is research funded and approved by federal agencies and departments that study, evaluate, improve or otherwise examine federal benefit programs which will be published on a list in accordance with 45 CFR § 46.104(5)(i) prior to the commencement of the research.
  7. Taste and Food Quality Research (see 45 CFR § 46.104(d)(6)) – this is research involving taste and quality of food which does not have additives or has ingredients/chemicals/contaminants at levels approved by the Food and Drug Administration, Environmental Protection Agency or Food Safety and Inspection Service.
  8. Storage/Maintenance of Secondary Research Requiring Consent (see 45 CFR § 46.104(d)(7))- this is research involving the storage and maintenance of secondary research of identifiable private information or identifiable bio specimens in which IRB will conduct the limited IRB review required in 45 CFR § 46.111(a)(8).
  9. Secondary Research Requiring Consent (see 45 CFR § 46.104(d)(8))- this is research involving identifiable private information or identifiable bio specimens for secondary research including each of the following:
    1. a.  Research in which broad consent in accordance with 45 CFR § 46.116(a)(1) was obtained;
    2. b.  Research in which documentation of informed consent or waiver of documentation of consent was obtained in accordance with 45 CFR § 46.117;
    3. c.  Researchers employ Weber State University IRB authorized data management procedures in compliance with the guidance from HHS on confidentiality of data in accordance with 45 CFR § 46.111(a)(7); and
    4. d.  IRB will make a determination whether the research is within the scope of the broad consent.

The Revised Common Rule has several differences in the exempt categories from the previous version. For a replete overview of the changes, the Federal Register provides a detailed description of the changes to the Common Rules’ exempt categories and the rationale for these changes. Also, OHRP provides a redline comparison between the Revised Common Rule and the previous regulation (see Redline Comparison).

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2.2 Classroom Research Activities

A faculty member responsible for the classroom research activities may elect to employ the processes described above in Sections 2.1 or 2.1.1. Alternatively, the faculty member may employ the process described in this Section 2.2. The faculty member may employ the process outlined in this section as long as each of the following conditions are met:

  1. The research is a classroom activity that is completed within the course of one semester (e.g. an assignment given to fulfill a classroom requirement, which does not include an undergraduate or masters’ degree cape stone project, thesis or dissertation, etc.);
  2. The research is intended primarily to instruct a student on research methods; and
  3. The research is exempt under the categories found in 45 CFR § 46.104, except 45 CFR § 46.104(d)(5), and does not require limited IRB review under 45 CFR § 46.111(a)(7) or 45 CFR § 46.111(a)(8).

If all these conditions are met, then the faculty member may elect to employ the short exempt form for the classroom research. In order to use this form, the faculty member interested in conducting exempt classroom activity research must do the following:

  1. Accurately mark all the check boxes, which correspond with the relevant categories of exempt research to be conducted as part of their classroom activities;
  2. Read the entire form and sign their names affirming that they agree to the terms of the form;
  3. Require all participating students to read the entire form and sign their names affirming that they agree to the terms of the form;
  4. The faculty member must submit this form electronically prior to commencing research in their courses as instructed by the form; and
  5. A faculty member, teaching multiple sections of the same course, only needs to submit one form with signatures from each student in their sections, but must not use the same form for different courses.

All other research must undergo the normal IRB process. However, a faculty member may submit one normal IRB form as a PI with their students listed as Co-PIs for nonexempt research as long as the classroom research activities are within the scope of the same research project.

In order to provide oversight and accountability, the IRB may review all classroom activity research through audits. By filling out this form, the faculty member agrees to retain reasonable records of the classroom activity research for three (3) years after the end of the research activities. The faculty member also agrees reasonably to work with the IRB committee to enable such review.

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2.3 FDA Exempt Categories

The FDA establishes the following four categories of research that are exempt from IRB review (see 21 CFR § 56.104):

  1. Research Commenced before July 27, 1981 and Still Subject to IRB Requirements before this Date (see 21 CFR § 56.104(a));
  2. Research Commenced before July 27, 1981 and Not Subject to IRB Requirements before this Date (see 21 CFR § 56.104(b));
  3. Emergency Use of Test Article (see 21 CFR § 56.104(c)); and
  4. Taste and Food Quality Evaluation and Consumer Acceptance Studies (see 21 CFR § 56.104(d));

The first two categories of FDA exempt research (see 21 CFR § 56.104(a-b)) are no longer applicable for research at the University. This is because at the time of amending these procedures no current research commenced before 1981. To qualify for the emergency use of test article exemption (see 21 CFR § 56.104(c)), the PI needs to demonstrate the following in written documentation:

  1. The use of a test article on a human subject was in a life-threatening situation in which no standard acceptable treatment was available, and in which there was not sufficient time to obtain IRB approval (see 21 CFR § 56.102(d));
  2. There was no previous use of the test article (see 21 CFR § 56.104(c)); and
  3. The emergency use was reported to the IRB within five (5) working days (see 21 CFR § 56.104(c)).

The PI needs to submit this written documentation to the designated IRB reviewer. Then the designated IRB reviewer will store this written documentation in the designated repository.

The criteria to qualify for the FDA exemption for the taste and food quality evaluation and consumer acceptance studies (see 21 CFR § 56.104(d)) are substantively the same as the criteria for the Common Rule exemption (see 45 CFR § 46.104(d)(4)). The PI and the IRB designated reviewer are responsible for following the procedures outlined above in Section 2.1.

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3. Conducting review at a meeting of the convened IRB

Section 3.1 begins with an overview of the convening of an IRB meeting. Section 3.2 outlines the process of submitting documents to the IRB committee members. Section 3.3 describes a timeline for receipt of submissions, scheduling IRB review, and document distribution to IRB members. Section 3.4 provides an overview of the reviewer system employed in the IRB at the convened meeting. Section 3.5 cursorily outlines the documents distributed to the IRB members. Section 3.6 concludes with a discussion of the possible actions that the IRB can take.

3.1 Convened Meeting

As required by 45 CFR § 46.108(b), the convening of an IRB meeting occurs when:

  1. A majority of the members of the IRB are present; and
  2. At least one member, whose primary concerns are in nonscientific areas, is present.

At the discretion of the IRB Chair and the vote of the majority IRB committee members, the Institutional Official may appoint alternate reviewers to stand in the place of the IRB committee members. Section 3.4 more fully describes the alternate reviewers.

For purposes of calculating whether there are a majority of the IRB members present, the number of primary IRB members present in the meeting and the alternates replacing any primary IRB member comprise the numerator. The total number of the primary reviewers comprises the denominator. Then the denominator divides the numerator to calculate whether a majority of IRB members are present (e.g. IRB Members Present (including replacing alternates) ÷ Total Number of Primary Reviewers). Accordingly, a majority of the members of the IRB are present when one the following occurs:

  1. More than fifty percent of the total primary reviewers are present at the IRB meeting; or
  2. Primary reviewers and one or more alternate reviewers, acting on behalf of the primary reviewers, are present at the IRB meeting and comprise more than fifty percent of the total primary reviewers.

For an IRB protocol to be approved, it must receive approval from a majority of the IRB members present at the meeting (see 45 CFR § 46.108(b)).

3.1.1 Electronic Meetings

Consistent with the IRB Meetings Convened via Telephone Conference Call: OPRR Memorandum (2000), IRB committee members may participate remotely in and be counted towards a majority for a convened IRB meeting through electronic means so long as the following occurs:

  1. Each participating IRB member “has received all the pertinent material prior to the meeting”; and
  2. These members “can actively and equally participate in the discussion of the protocols” (see OPRR Memorandum (2000)).

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3.2 Submitted Documents

The PI is responsible for submitting the following documentation for an IRB meeting:

  1. A fully completed Application of the Use Of Human Subjects form;
  2. An informed consent statement as required by 45 CFR § 46.116 unless the PI justifies why an informed consent statement inhibits his/her research in accordance with 45 CFR § 46.117;
  3. A certificate of completion of the CITI Program training at least within the past three years of the proposed research or a comparable training approved by the IRB Chair; and
  4. Any other supplemental documentation such as recruitment materials or documentation as reasonably requested by the designated IRB reviewer or the IRB committee.

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3.3 Timelines

Once a designated IRB reviewer determines that a protocol requires full board review, the IRB reviewer should timely notify the IRB Chair of this determination. The reviewer should provide all the documentation outlined in Section 3.2 to the IRB Chair. The IRB Chair and IRB staff must timely provide the documentation outlined in Section 3.2 to all IRB committee members. Then the IRB Chair should timely schedule an IRB meeting. Unless impracticable, the IRB meeting will schedule a meeting at least ninety (90) days from the time that the IRB Chair received notice that the protocol requires full board review. The IRB will schedule meetings as needed.

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3.4 Reviewer System

The IRB reviewer system currently only includes primary reviewers. However, the majority of the IRB committee members at a convened meeting may vote to create alternate reviewers. The Institutional Official may then appoint alternate reviewers to replace primary reviewers who may not be able to attend IRB committee meetings. Upon adopting the use of the alternate reviewers, the IRB must develop and document procedures to deal with the following issues related to alternate reviewers:

  1. Whether any alternate can replace any committee member so long as at least one member, whose concerns are in nonscientific areas, is present in the IRB meeting;
  2. Who requests that the alternate replace a primary member;
  3. Under what conditions may an alternate replace a primary member; and
  4. What notice is sufficient to communicate that an alternate reviewer is authorized to replace a primary reviewer not present in the IRB meeting.

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3.5 Document Distributed

The IRB will provide all the documents submitted, as outlined in Section 3.2, to all primary reviewers and alternate reviewers, as applicable. This document distribution will facilitate the full participation and review of all the IRB members.

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3.6 Range of Possible Actions

As proscribed in 45 CFR § 46.109(a), the Common Rule authorizes the convened IRB committee to take a number of actions on research proposals. These actions include approve, require modifications in (to secure approval), and disapprove the research activities. The Common Rule further authorizes the convened IRB committee to suspend or terminate research that has not been conducted “in accordance with the IRB’s requirements or that has been associated with unexpected serious harm” to the research participants (see 45 CFR § 46.113). The IRB committee will notify a PI of its decisions outlined in this Section 3.6 in writing as required by 45 CFR § 46.109(d) and 45 CFR § 46.113. A more detailed description of the possible actions for protocols reviewed under full board review follows:

  1. Approved: The IRB may approve the protocol as submitted. The approval is valid for the period specified in the correspondence to the PI. The IRB determines the date of the continuing review (expiration of approval) for full reviewed. The continuing review may not exceed three hundred and sixty-four (364) days from the IRB approval of the protocol. The period of approval duration is based on a number of items including but not limited to: the level of risk, the nature of the research, or the population. The period of the approval may be significantly less than the maximum period allowed by regulation.
  2. Approved as Modified by the IRB: The IRB may approve the protocol with revisions, clarifications or other changes. The IRB may require these changes in the protocol, the informed consent, or other documents. The approval is valid for the period specified in the correspondence to the PI. The IRB determines the date of the continuing review (expiration of approval) for full reviewed studies. This applies even if the approval is contingent upon revisions or corrections. The continuing review may not exceed three hundred and sixty-four (364) days from the IRB approval of the protocol. If the PI does not concur with the changes made by the IRB, he/she may not initiate the study. The IRB approval is void. The PI may: withdraw the study, appeal to the IRB in accordance with the Policy Procedure Manual (PPM) 4-34b, or make revisions to the study for review by the IRB. The PI may not start the study until the IRB approves the protocol as the PI intends to conduct the study.
  3. Deferred for Expedited Review by the IRB Chair or their Designee (Approved with Conditions): The IRB approved the protocol, but with conditions that require revisions and/or clarifications. These revisions and/or clarifications are non-substantive, minor, and not directly relevant to the IRB determinations required under 45 CFR § 46.111 and 21 CFR § 56.111. The IRB may review and approve such revisions or clarifications through the IRB Chair or his/her designee on an expedited basis. The IRB will clearly specify the action(s) needed and who has the authority to conduct the review. The IRB Chair at his/her discretion may return the revised protocol for review at a convened meeting of the IRB. The PI must submit the required revisions or clarifications to the IRB office within six (6) months following notification. If the IRB does not receive the revisions or clarifications within six (6) months, the IRB approval is void. Once this occurs, the PI will need to resubmit the protocol for review at a convened meeting of the IRB.
  4. Disapproved: The IRB will disapprove the proposed research. The IRB may disprove research when: the research does not have a reasonable relationship between the risks and anticipated benefits; it has inequitable subject selection; it does not appropriately provide for informed consent/assent; it does not safeguard data and have adequate provisions to protect patient confidentiality; or it raises such ethical questions as to be unacceptable.
  5. Tabled: During full board meetings, the IRB may table a protocol when: questions about the protocol are substantial; there is an indeterminate level of risk; the study requires major revisions; and the IRB is unable to review and/or vote on the protocol. The IRB will return the tabled protocol to the PI to address the IRB's concerns. The IRB may table a protocol if there is not sufficient time to complete a comprehensive review of the study. In this instance, the IRB will prioritize the review of the protocol during the next convened meeting.

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4. Conducting review via expedited review procedures

Section 4.1 starts with an overview of whether a proposal meets the requirements for expedited review. Section 4.2 provides a description of the documents submitted to the IRB committee members. Section 4.3 describes a timeline for receipt of submissions and scheduling the expedited review. Section 4.4 provides an overview of who confirms the study qualifies for expedited review and conducts that expedited review. Section 4.5 cursorily outlines the possible actions taken by IRB. Section 4.6 concludes with an overview of the method for keeping all members advised of research proposals approved via the expedited review.

4.1 Qualifies for Expedited Review

Expedited Review is appropriate under the following conditions:

  1. The research falls under one of the expedited categories published as a Notice in the Federal Register by the Secretary of HHS and involves no more than minimal risk (see 45 CFR § 46.110(b)(1)(i));
  2. The research involves minor changes in previously approved research during the period for which the research is approved (see 45 CFR § 46.110(b)(1)(ii); and
  3. The limited review for 45 CFR § 46.104(f) exempt research (see 45 CFR § 46.110(b)(1)(iii)).

The current expedited categories published as a Notice in the Federal Register include the following:

  1. Clinical studies of drugs and medical devices only when condition so long as the following:
    1. 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.); and
    2. 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, heal-stick, ear-stick, or venipuncture as follows:
    1. 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 8-week period and collection may not occur more frequently than 2 times per week; or
    2. 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 8-week period and collection may not occur more frequently than 2 times per week.
  3. Prospective collection of biological specimens for research purposes by noninvasive means. Examples include: (a) hair and nail clippings in a nondisfiguring 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) supragingival 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; and (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 include: (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; and (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 from further review and thus not qualifying for center level review.)
  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:
    1. 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
    2. b. where no subjects have been enrolled and no additional risks have been identified; or
    3. 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 two (2) through eight (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.

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4.2 Submitted Documents

The PI is responsible for submitting the following documentation to a designated IRB reviewer:

  1. A fully completed application of the use of human subject’s form;
  2. An informed consent statement as required by 45 CFR § 46.116 unless the PI justifies why an informed consent statement inhibits his/her research in accordance with 45 CFR § 46.117;
  3. A certificate of completion of CITI Program training at least within the past three (3) years of the proposed research or a comparable training approved by the IRB Chair; and
  4. Any other supplemental documentation such as recruitment materials or documentation as reasonably requested by the designated IRB reviewer or the IRB committee.

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4.3 Timelines

Upon the receipt of the documentation in Section 4.2, the IRB reviewer will use his/her reasonable efforts to review the research protocol within ten (10) business days. The IRB reviewer will make a determination of whether the research qualifies for expedited review. The IRB reviewer may provide feedback on the research proposal. Upon making the expedited determination, the IRB reviewer will send the proposal to any other IRB member. This other IRB member will use his/her reasonable efforts to review the research protocol within ten (10) business days and provide any additional feedback. Upon a dispute between the reviewers, the IRB Chair will make the determination of whether the research qualifies for expedited review. These timelines are aspirational. The expedited review time may require more time when the reviewers are reviewing multiple research protocols or have other professional responsibilities.

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4.4 Expedited Review Process

The expedited review process begins when a PI sends the documents outlined in Section 4.2 to a designated IRB reviewer. The PI may suggest to the reviewer that he/she believes that the research qualifies for expedited review. However, the designated IRB reviewer is primarily responsible for this determination. Once the designated IRB reviewer makes this determination and provides any suggested modifications to the research proposal, the designated IRB reviewer sends the documents with his/her edits and the expedited determination to any other IRB committee member. The IRB committee member will then review the documents and make any modifications. If there is a disagreement between IRB members on the expedited review determination, the IRB Chair will determine whether the research qualifies for expedited review.

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4.5 Range of Possible Actions

As proscribed in 45 CFR § 46.110(b), the Common Rule authorizes the IRB to approve and require modifications in (to secure approval) all research activities. However, the IRB may not disapprove the research for the expedited review process. The designated IRB reviewer will notify PIs of his/her decisions outlined in this Section 4.4 in writing as required by 45 CFR § 46.109(d) and 45 CFR § 46.113. A more detailed description of the possible actions for protocols reviewed under expedited review follows:

  1. Approved: The IRB reviewer approves the protocol as submitted under the expedited review process. The approval is valid for the period specified in the correspondence to the PI. The IRB reviewer will base the period of approval on the level of risk, the nature of the research, or the population. Unless required by the IRB reviewer, continuing review is not required under the expedited review process (see 45 CFR § 46.109(f)(1)(i)). If continuing review is required, the IRB reviewer will determine the date of the continuing review, which may not exceed three hundred and sixty-four (364) days.
  2. Approved as Modified by the IRB: The IRB reviewer approves the protocol with revisions, clarifications or other changes. The IRB may require these changes to the protocol, the informed consent, or other documents. The approval is valid for the period specified in the correspondence to the PI. Unless required by the IRB reviewer, continuing review is not required under the expedited review process (see 45 CFR § 46.109(f)(1)(i)). If continuing review is required, the IRB reviewer will determine the date of the continuing review, which may not exceed three hundred and sixty-four (364) days. If the PI does not concur with the changes made by the IRB, he/she may not initiate the study pursuant to the IRB approval. The IRB approval is void. The PI may withdraw the study, appeal to the IRB, or revise the study for review by the IRB. The PI may not start the study until the IRB approves the protocol as the PI intends to conduct the study.
  3. Deferred for Re-Review by the Convened IRB: The IRB reviewer does not approve the protocol. The IRB determines that the convened IRB will need to review the proposal. This motion is applicable when the IRB reviewer has determined that the nature of the protocol does not meet the requirements of expedited review.
  4. Tabled: During expedited reviewer, the IRB reviewer may table a protocol when: questions about the protocol are substantial; the level of risk cannot be ascertained; the submission of documents is inadequate; and the study requires major revisions. The IRB reviewer will table the protocol. The IRB reviewer will return the protocol to the PI to address the concerns.

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5. Determining that the criteria for IRB approval of research are met

The IRB Committee is responsible for devising mandatory forms. The forms should elicit information relevant to whether the IRB should approve a research proposal. The PI is responsible for ensuring that the questions are sufficiently answered. The IRB may at its sole discretion require the PI and Co-PI to provide additional information or require more detailed and thorough answers to the questions in the mandatory forms. More specifically, the IRB will design the mandatory forms, which include the following factors as required by 45 CFR § 46.111:

  1. Risks to subjects are minimized by sound research design, not unnecessarily exposing subjects to risks, and using, where appropriate, procedures already being used to treat and/or diagnosis the subjects (see 45 CFR § 46.111(a)(1));
  2. Risks to subjects are reasonable in relation to the anticipated benefits to the subjects and/or the importance of the knowledge that may be expected to result from the research (see 45 CFR § 46.111(a)(2));
  3. Selection of subjects is equitable in consideration of the setting and/or purpose of the research (e.g. does the research involve subjects vulnerable to coercion; see 45 CFR § 46.111(a)(3));
  4. Informed consent from research subjects or their legally authorized representatives will be sought in accordance with 45 CFR § 46.116 (see 45 CFR § 46.111(a)(4));
  5. Informed consent will be documented in accordance with 45 CFR § 46.117 (see 45 CFR § 46.111(a)(5));
  6. Where appropriate, the research plan makes adequate provisions for monitoring the data collected to ensure the safety of subjects (see 45 CFR § 46.111(a)(6));
  7. There are adequate provisions to maintain the privacy and confidentiality of the subjects and data in accordance with the standards in 45 CFR § 46.105 or exceeding these standards based on the sensitivity of the data (see 45 CFR § 46.111(a)(7)); and
  8. The PIs and/or Co-PIs have an appropriate plan to return clinically relevant results to subjects in instances where they intend to share these results (see 45 CFR § 46.111(a)(8)).

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6. Reviewing and approving the informed consent form and informed consent process

Section 6.1 starts with an overview of how the IRB ensures that all of the required elements of consent, and any additional elements of consent are included in informed consent forms. Section 6.2 discusses the document control system used by the IRB to assist the PI and study staff in presenting subjects with the current IRB-approved consent form. Section 6.3 describes how the IRB reviews the informed consent process and assesses provisions for translations of the informed consent form for non-English speaking subjects, when applicable. Section 6.4 provides an overview of how the IRB determines whether the IRB-approved informed consent form requires revision at the time of continuing review. Section 6.5 describes the IRB process for approving waivers or alterations of the consent procedure regulated by the Common Rule. Section 6.6 concludes with a discussion of the IRB’s process for approving waivers of documentation of consent.

6.1 Required Elements of Consent

The PI is required to submit informed consent forms in keeping with University requirements and federal regulations. Upon request, the IRB will provide a model informed consent form to assist a PI in completing consent forms. A consent form may be either:

  1. A written consent document that embodies the elements of informed consent noted above. This form may be read to the subject or the subject's legally authorized representative, but in any event, the PI will give either the subject or the representative adequate opportunity to read it before it is signed (see 45 CFR § 46.117(b)(1); or
  2. The IRB may approve a short form written consent document stating that the elements of informed consent noted above have been presented orally to the subject or the subject's legally authorized representative. When this method is used, there will be a witness to the oral presentation. Also, the IRB will approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness will sign both the short form and a copy of the summary, and the person actually obtaining consent will sign a copy of the summary. A copy of the summary will be given to the subject or the representative, in addition to a copy of the short form (see 45 CFR § 46.117(b)(2)).

The PI is responsible for specifically addressing whether general requirements of consent are met. IRB reviewers are responsible for reviewing consent forms and ensuring that these general requirements are met. The IRB may require elements in the informed consent that exceed the requirements of the OHRP and the FDA. Additionally, a PI will need to comply with any applicable law, pertaining to consent within a particular jurisdiction. The IRB may require PIs to provide documentation with respect to local consent laws and develop procedures to comply with these laws. For research regulated by the Common Rule, the general requirements of consent are the following (see 45 CFR § 46.116(a)):

  1. Before involving a human subject in research covered by this policy, an investigator will obtain the legally effective informed consent of the subject or the subject’s legally authorized representative.
  2. An investigator will seek informed consent only under circumstances that provide the prospective subject or the legally authorized representative sufficient opportunity to discuss and consider whether or not to participate and that minimize the possibility of coercion or undue influence.
  3. The information that is given to the subject or the legally authorized representative will be in language understandable to the subject or the legally authorized representative.
  4. The prospective subject or the legally authorized representative 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, and an opportunity to discuss that information.
  5. Except for broad consent obtained, informed consent must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research. This part of the informed consent must be organized and presented in a way that facilitates comprehension. Informed consent as a whole must present information in sufficient detail relating to the research, 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 or legally authorized representative’s understanding of the reasons why one might or might not want to participate.
  6. No informed consent may include any exculpatory language through which the subject or the legally authorized representative is made to waive or appear to waive any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.

As regulated by the FDA the general requirements of consent are the following (see 21 CFR § 50.20):

Except as provided in Title 21 Sections 50.23 and 50.24, no investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An investigator will seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject or the representative will be in language understandable to the subject or the representative. No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.

The IRB will ensure that the general elements of informed consent as defined by the OHRP and the FDA are included. In accordance with 45 CFR § 46.116(b) and 21 CFR § 50.25, the consent document must contain the following elements:

The IRB will ensure that the general elements of informed consent as defined by the OHRP and the FDA are included. In accordance with 45 CFR § 46.116(b) and 21 CFR § 50.25, the consent document must contain the following elements:

  1. Information about the research including a statement that the study involves research, an explanation of the purpose(s) of the research, the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;
  2. A description of any reasonably foreseeable risks or discomforts to the subject;
  3. A description of any benefits to the subject or to others which may reasonably be expected from the research;
  4. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
  5. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
  6. For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;
  7. An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject;
  8. A 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;
  9. For research involving FDA regulated drug (including biological products) and device clinical trials (should the University ever engage in such trials), the following specific statement that clinical trial information will be entered into a databank must be included in the consent form. Submission of clinical trial information to the NIH/National Library of Medicine data bank is required by statute. The statement is to be included in the applicable section that discusses the extent to which confidentiality is to be maintained. The statement is as follows: -A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not include information that can identify you. At most, the website will include a summary of the results. The website will be maintained by the IRB Compliance Officer; and
  10. For research regulated under the Common Rule, one of the following statements about any research that involves the collection of identifiable private information or identifiable biospecimens: (i) A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the legally authorized representative, if this might be a possibility; or (ii) A statement that the subject’s information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies.

When appropriate, one or more of the following elements of informed consent will also be provided:

  1. A 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;
  2. Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;
  3. Any additional costs to the subject that may result from participation in the research.
  4. The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;
  5. A 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;
  6. The approximate number of subjects involved in the study;
  7. For Common Rule regulated research, a statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit;
  8. For Common Rule regulated research, a statement regarding whether clinically relevant research results, including individual research results, will be disclosed to subjects, and if so, under what conditions; and
  9. For Common Rule regulated research which involves biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).
6.1.1 Elements of Broad Consent

Under the Revised Common Rule, the drafting agencies created the broad consent (see 45 CFR § 46.116(d)). PIs may use broad consent as an alternative to informed consent outlined in 45 CFR § 46.116(b-c) for the following types of research:

  1. Storage,
  2. Maintenance, and
  3. Secondary research use of identifiable private information or identifiable biospecimens (collected for either research studies other than the proposed research or nonresearch purposes).

In order to receive broad consent, the PI will provide to each subject or his/her legally authorized representative the following:

  1. A description of any reasonably foreseeable risks or discomforts to the subject;
  2. A description of any benefits to the subject or to others which may reasonably be expected from the research;
  3. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
  4. A 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;
  5. When appropriate, a statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit;
  6. When appropriate, for research which involves biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen);
  7. A general description of the types of research that may be conducted with the identifiable private information or identifiable biospecimens. This description must include sufficient information such that a reasonable person would expect that the broad consent would permit the types of research conducted;
  8. A description of the identifiable private information or identifiable biospecimens that might be used in research, whether sharing of identifiable private information or identifiable biospecimens might occur, and the types of institutions or researchers that might conduct research with the identifiable private information or identifiable biospecimens;
  9. A description of the period of time that the identifiable private information or identifiable biospecimens may be stored and maintained (which period of time could be indefinite), and a description of the period of time that the identifiable private information or identifiable biospecimens may be used for research purposes (which period of time could be indefinite);
  10. Unless the subject or legally authorized representative will be provided details about specific research studies, a statement that they will not be informed of the details of any specific research studies that might be conducted using the subject’s identifiable private information or identifiable biospecimens, including the purposes of the research, and that they might have chosen not to consent to some of those specific research studies;
  11. Unless it is known that clinically relevant research results, including individual research results, will be disclosed to the subject in all circumstances, a statement that such results may not be disclosed to the subject; and
  12. An explanation of whom to contact for answers to questions about the subject’s rights and about storage and use of the subject’s identifiable private information or identifiable biospecimens, and whom to contact in the event of a research-related harm.

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6.2 Documentation Control System

The IRB will post its current consent form template on its webpage to assist the PI to draft consent forms. Once the IRB reviewers approve the consent form as drafted or with modifications, the PI is responsible to ensure that the research team provides the research subjects with the approved consent form.

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6.3 Translations and Translation Services

The IRB Chair may appoint individuals who are sufficiently fluent in non-English languages to review consent forms in these languages. These individuals are responsible to determine whether non-English informed consent forms conform to their respective English versions. These individuals may not be associated with the study nor have contributed to the original translations. Colleges may also appoint persons, qualified to perform these services. If there are no such appointed translators, the PI must submit consent materials translated by a certified translator. The IRB may maintain a list of the translators appointed by the IRB Chair. The IRB does not require the translation of the informed consent document until the IRB approves the English language version.

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6.4 Continuing Review

At the time of continuing review, the PI must submit a copy of the informed consent document to the IRB. The IRB will verify that the PI is using the most recently approved version of the consent document. The IRB will ensure that the consent document contains accurate and up-to-date information about the research.

If the IRB waived the signed consent document requirement (45 CFR § 46.117(c)), the IRB will assess the accuracy of the oral communications to the subjects. The IRB will also assess any written statements provided to the subjects.

When reviewing an informed consent document, the IRB will ensure that the currently approved or proposed consent document adequately addresses the elements of informed consent required under 45 CFR § 46.116(a) and (b). The IRB will determine:

  1. Whether the informed consent document provides an accurate and up-to-date description of the reasonably foreseeable risks and discomforts of the research to the subjects (45 CFR § 46.116(a)(2)); and
  2. Any appropriate alternative procedures or courses of treatment that might be advantageous to the subject (45 CFR § 46.116(a)(4)).

Based on any new information discovered in continuing review, the IRB will assess whether the informed consent process allows for:

  1. Adequate opportunities for research participants to discuss the information;
  2. Sufficient opportunities for research participants to review information that a reasonable person would want to have to make an informed decision; and
  3. Adequate procedures to minimize the possibility of coercion or undue influence (see 45 CFR § 46.116).

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6.5 Alteration of Consent Procedures

In accordance with 45 CFR § 46.116(e), the IRB may alter or waive consent for public benefit programs. The scope of this waiver and alteration apply to the elements of the Section 6.1 except for the broad consent outlined in Section 6.1.1. For this public benefit programs alternation and waiver to apply, the following must occur:

  1. The IRB finds and documents that the research could not practicably be carried out without the waiver alteration; and
  2. The research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine:
    1. i. Public benefit or service programs;
    2. ii. Procedures for obtaining benefits or services under those programs;
    3. iii. Possible changes in or alternatives to those programs or procedures; or
    4. iv. Possible changes in methods or levels of payment for benefits or services under those programs; and
    5. v. The research could not practicably be carried out without the waiver or alteration.

In accordance with 45 CFR § 46.116(f), the IRB may alter or waive consent in general if certain conditions are met. The scope of this waiver and alteration apply to the elements outlined in Section 6.1 except for the broad consent outlined in Section 6.1.1. The IRB can grant alteration/waiver of informed consent if it is determined that:

  1. The research involves no more than minimal risk to the subjects;
  2. The research could not practicably be carried out without the requested waiver or alteration;
  3. If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format;
  4. The waiver or alteration will not adversely affect the rights and welfare of the subjects; and
  5. Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation.

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6.6 Waiver of Requirement for Signed Informed Consent

In accordance with 45 CFR § 46.117(c), the IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds any of the following:

  1. That 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;
  2. That 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. If the subjects or legally authorized representatives are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to subjects and provided there is an appropriate alternative mechanism for documenting that informed consent was obtained.

As proscribed in 45 CFR § 46.117(c)(2), in cases in which the documentation requirement is waived, the IRB may require the PI to provide subjects or legally authorized representatives with a written statement regarding the research. This only waives the requirement that the research participant sign the informed consent. This research participant still must:

  1. Consent to participate;
  2. Be given appropriate information about the study; and
  3. Have the ability to decline participation without repercussions.

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7. Describing how the IRB decides whether additional safeguards should be put in place when the study involves subjects who are likely to be vulnerable to coercion or undue influence

The Revised Common Rule states:

An investigator will seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to discuss and consider whether or not to participate and that minimize the possibility of coercion or undue influence (45 CFR § 46.116(a)(2)).

OHRP has not authored an opinion on what the terms “coercion” or “undue influence” mean although there are commonly accepted legal definitions for these terms.

Informed consent is a relatively nascent legal construct originating from contract law before becoming rooted in tort law. This provenance makes contract law relevant to understand the concepts of coercion and undue influence in the context of informed consent. In some jurisdictions, courts have held that coercion is an element of the doctrine of duress in contract law. The Restatement (Second) of Contracts § 176 defines duress in the following manner:

  1. If a party's manifestation of assent is induced by an improper threat by the other party that leaves the victim no reasonable alternative, the contract is voidable by the victim.
  2. 2. If a party's manifestation of assent is induced by one who is not a party to the transaction, the contract is voidable by the victim unless the other party to the transaction in good faith and without reason to know of the duress either gives value or relies materially on the transaction.

The Restatement (Second) of Contracts § 177 defines when a threat is improper in the following manner:

  1. A threat is improper if
    1. (a) what is threatened is a crime or a tort, or the threat itself would be a crime or a tort if it resulted in obtaining property,
    2. (b) what is threatened is a criminal prosecution,
    3. (c) what is threatened is the use of civil process and the threat is made in bad faith, or
    4. (d) the threat is a breach of the duty of good faith and fair dealing under a contract with the recipient.
  2. A threat is improper if the resulting exchange is not on fair terms, and
    1. (a) the threatened act would harm the recipient and would not significantly benefit the party making the threat,
    2. (b) the effectiveness of the threat in inducing the manifestation of assent is significantly increased by prior unfair dealing by the party making the threat, or
    3. (c) what is threatened is otherwise a use of power for illegitimate ends.

Duress or coercion is most likely to arise in an IRB context in the following scenarios:

  1. When there is a threat which breaches a duty of good faith and fair dealing under a contract with the recipient; or
  2. Where the exchange is not on fair terms and what is threatened is otherwise a use of power for illegitimate ends.

This coercion may occur when a health care provider threatens to discontinue providing health care unless a patient consents to participate in a research protocol. This would breach the express or at least implied contract of good faith and fair dealing assumed by the health care provider by treating the patient. It, also, would be a use of power for illegitimate ends. Similarly, a faculty member or employer may breach a duty of good faith and fair dealing resulting from the student code (see University Policy and Procedure Manual (PPM) 6-22) or the employment contract. This breach would occur if faculty or employer threaten a student or employee with a penalty unless the student or employee participate in a research protocol. These relationships may also be duress because the “exchange is not on fair terms”; and the employer and faculty member may be using their “power for illegitimate ends.”

Although duress is possible, undue influence is more likely to occur in an IRB context. The Restatement (Second) of Contracts § 178 defines undue influence in the following manner:

  1. Undue influence is unfair persuasion of a party who is under the domination of the person exercising the persuasion or who by virtue of the relation between them is justified in assuming that that person will not act in a manner inconsistent with his welfare.
  2. If a party's manifestation of assent is induced by undue influence by the other party, the contract is voidable by the victim.
  3. If a party's manifestation of assent is induced by one who is not a party to the transaction, the contract is voidable by the victim unless the other party to the transaction in good faith and without reason to know of the undue influence either gives value or relies materially on the transaction.

Undue influence occurs when someone has a position of power or influence over another person. This power or influence induces the other person to act against his/her own interest. This is likely to occur when person in a supervisory role (e.g. faculty, employer, prison guard, etc.) induces the participation of a person in a subservient role (e.g. student, employee, prisoner, etc.) to participate in research.

While it may not likely be recognized as undue influence or coercive under the Restatement (Second) of Contracts, compensation or incentives for participating in research may impair a participant’s ability to fully consent. Because payment is generally not viewed as coercive, IRB does not consider payment ipso facto to be an instance of undue influence or coercion. However, it may occur where a study targets a population who is impoverished or otherwise vulnerable. In vulnerable populations, payment may induce participation in research even though this participation is substantively not in the participants’ best interest.

Because of the aforementioned reasons, the IRB will consider the following criteria:

  1. Whether there is compensation for participating in the research;
  2. Whether the PI is in a position of power relative to the research participant (e.g. student’s involvement in faculty research);
  3. Whether there is the participation of vulnerable populations such as minors, the elderly, the cognitively impaired, prisoners, and pregnant women;
  4. The likelihood the participant would consent to participate in the research absent the incentive or compensation;
  5. The risk involved in the research; and
  6. The relative benefits granted by the incentive or compensation to the potential participants.

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8. Reviewing any study requesting an Exception from Informed Consent Requirements for Emergency Research

Given the nature of the research at the University, it is unlikely that an exception from informed consent for emergency research would occur. However to comply with the requirements of 21 CFR § 50.24, the IRB will rely upon the “Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors Exception from Informed Consent Requirements for Emergency Research” for its processes and procedures (see Guidance for Emergency Research). In accordance with this FDA guidance document, the IRB must first find and document the following:

  1. The research involves subjects unable to consent;
  2. The research is subject to FDA’s regulations and will be carried out under an FDA Investigational New Drug Application (IND) or an FDA Investigational Device Exemption (IDE).

Second, the IRB will find and document that the requirements for exception from informed consent for emergency research detailed in 21 CFR § 50.24 have been met including:

  1. The human subjects are in a life-threatening situation, available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence, which may include evidence obtained through randomized placebo-controlled investigations, is necessary to determine the safety and effectiveness of particular interventions.
  2. Obtaining informed consent is not feasible because:
    1. i. The subjects will not be able to give their informed consent as a result of their medical condition;
    2. ii. The intervention under investigation must be administered before consent from the subjects' legally authorized representatives is feasible; and
    3. iii. There is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the clinical investigation.
  3. Participation in the research holds out the prospect of direct benefit to the subjects because:
    1. i. Subjects are facing a life-threatening situation that necessitates intervention;
    2. ii. Appropriate animal and other preclinical studies have been conducted, and the information derived from those studies and related evidence support the potential for the intervention to provide a direct benefit to the individual subjects; and
    3. iii. Risks associated with the investigation are reasonable in relation to what is known about the medical condition of the potential class of subjects, the risks and benefits of standard therapy, if any, and what is known about the risks and benefits of the proposed intervention or activity.
  4. The clinical investigation could not practicably be carried out without the waiver.
  5. The proposed investigational plan defines the length of the potential therapeutic window based on scientific evidence, and the investigator has committed to attempting to contact a legally authorized representative for each subject within that window of time and, if feasible, to asking the legally authorized representative contacted for consent within that window rather than proceeding without consent. The investigator will summarize efforts made to contact legally authorized representatives and make this information available to the IRB at the time of continuing review.
  6. The IRB has reviewed and approved informed consent procedures and an informed consent document consistent with 50.25. These procedures and the informed consent document are to be used with subjects or their legally authorized representatives in situations where use of such procedures and documents is feasible. The IRB has reviewed and approved procedures and information to be used when providing an opportunity for a family member to object to a subject's participation in the clinical investigation consistent with paragraph (a)(7)(v) of this section.
  7. Additional protections of the rights and welfare of the subjects will be provided, including, at least:
    1. i. Consultation (including, where appropriate, consultation carried out by the IRB) with representatives of the communities in which the clinical investigation will be conducted and from which the subjects will be drawn;
    2. ii. Public disclosure to the communities in which the clinical investigation will be conducted and from which the subjects will be drawn, prior to initiation of the clinical investigation, of plans for the investigation and its risks and expected benefits;
    3. iii. Public disclosure of sufficient information following completion of the clinical investigation to apprise the community and researchers of the study, including the demographic characteristics of the research population, and its results;
    4. iv. Establishment of an independent data monitoring committee to exercise oversight of the clinical investigation; and (v) If obtaining informed consent is not feasible and a legally authorized representative is not reasonably available, the investigator has committed, if feasible, to attempting to contact within the therapeutic window the subject's family member who is not a legally authorized representative, and asking whether he or she objects to the subject's participation in the clinical investigation. The investigator will summarize efforts made to contact family members and make this information available to the IRB at the time of continuing review.

In addition, the IRB must find that the study meets the relevant requirements of 21 CFR Parts 50 and 56.

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9. For FDA-regulated research, assessing whether the investigator and/or the sponsor determined that an IND or IDE is required for the proposed study if applicable, and the basis for this determination

Section 9.1 outlines the procedures to determine whether an Investigational New Drug (IND) is necessary. Section 9.2 describes the process to determine whether an Investigational Device Exemption (IDE) is necessary.

9.1 IND

Given the nature of the research at the University, it is unlikely that an IND will be necessary. However to comply with the requirements of 21 CFR § 312, the IRB will rely upon the “Guidance for Clinical Investigators, Sponsors, and IRBs Investigational New Drug Applications (INDs) —Determining Whether Human Research Studies Can Be Conducted Without an IND” for its processes and procedures (see Guidance on IND). IRB reviewers ought to consult with the IRB Chair and Compliance Officer to ensure that the IRB review of IND related research is conducted properly.

PIs, who will assume both the sponsor and investigator role, may review Investigational New Drug Applications Prepared and Submitted by Sponsor-Investigators Guidance for Industry (see Guidance for Sponsor-Investigators). These PIs may additionally seek external consultation from experts in FDA compliance.

The sponsor or PI may need to obtain an FDA IND when: a proposed research activity involves the evaluation of an investigational drug or biological material in humans; or before a FDA-approved drug can be used for unapproved indications. Whenever possible, the PI or sponsor should obtain an IND before IRB review. The PI must understand that by obtaining and holding an IND he/she assumes sponsor and investigator responsibilities for the conduct of the research as described in 21 CFR § 312.

If the research involves the use of a food, nutritional or food supplement that might fit the FDA definition of a “drug,” the IRB reviewer will review the protocol to determine whether the research involves the use of a drug as defined by FDA. Generally, bioavailability and bioequivalence studies are exempt from the IND requirements. The FDA defines a drug as:

  1. An article recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and
  2. An article intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and
  3. An article (other than food) intended to affect the structure or any function of the body of man or other animals; and
  4. An article intended for use as a component of any article specified in the numbered statements 1, 2 and 3 above.

If an IND is required, the study sponsor generally obtains the IND number. The PI should request the IND number from the sponsor and include the IND number within his/her protocol. The PI should also provide the IRB evidence corroborating the IND number including communication from the sponsor or a copy of the letter from the FDA to the sponsor. The IRB primary reviewer will verify the IND number included in the protocol with one of these corroborating sources. If the PI of the study holds the IND, then the PI should submit a copy of the communication from the FDA noting the IND number with the protocol submission. When completing the application, the PI must provide any research and other related information about the drug to the IRB. The PI should describe the storage, preparation, and dispensing of the investigational drugs in the protocol.

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9.2 IDE

Given the nature of the research at the University, it is unlikely that an IDE will be necessary. However to comply with the requirements of 21 CFR § 812, the IRB will rely upon the “FDA Categorization of Investigational Device Exemption (IDE) Devices to Assist the Centers for Medicare and Medicaid Services (CMS) with Coverage Decisions - Guidance for Sponsors, Clinical Investigators, Industry, Institutional Review Boards, and Food and Drug Administration Staff” for its processes and procedures (see Guidance IDE https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM504091.pdf). IRB reviewers ought to consult with the IRB Chair and Compliance Officer to ensure that the IRB review of IDE related research is properly conducted.

If a research activity uses a device for an indication for which the FDA has not cleared the device, the IRB reviewer will review FDA regulations to verify that the research meets the definition of a device investigation. Device studies must satisfy one of the following:

  1. Have an IDE approved by the FDA under 21 CFR § 812.30;
  2. Be categorized as fitting abbreviated requirements under 21 CFR § 812.2(b) or;
  3. Be deemed by the FDA as being exempt from the requirement to have an IDE under 21 CFR § 812.2(c).

By reviewing the protocol, some form of communication from the sponsor or a letter from the FDA to the sponsor, the IRB primary reviewer will determine whether the study has a FDA approved and issued IDE. If not, the IRB reviewer will determine whether the study meets the requirements for an abbreviated IDE or exemption from the requirement for an IDE.

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10. For FDA-regulated medical device research, making and documenting the significant/nonsignificant risk (SR/NSR) determination

Given the nature of the research at the University, it is unlikely that the IRB will need to make significant/nonsignificant risk (SR/NSR) determinations of medical devices. However, to comply with the requirements of 21 CFR § 812, the IRB will rely upon the “Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors Significant Risk and Nonsignificant Risk Medical Device Studies” for its processes and procedures (see Guidance SR/NSR https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126418.pdf).

If a PI or sponsor claims a device is not a significant risk, then the IRB will review the research involving the investigational device at a convened meeting. The IRB will determine whether the study using the device is a significant risk, within the context of the overall study, by reviewing the criteria in 21 CFR § 812.3(m). A significant risk device means that the device:

  1. Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
  2. Is purported or represented to be for use supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
  3. Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
  4. Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

A non-significant risk device study is one that does not meet the definition for a significant risk device study.

If the IRB determines that the study using the device is not a “significant risk,” it will document that determination in the minutes, along with the IRB’s rationale for that decision. The IRB will notify the PI of its determination and the study may begin without submission of an IDE application to the FDA.

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

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11. For HHS-conducted or -supported research, determining the applicability of additional protections for Pregnant Women, Human Fetuses and Neonates, and for Prisoners, found in 45 CFR 46 Subparts B and C respectively

Section 11.1 discusses the additional protections for pregnant women, human fetuses and neonates provided under 45 CFR Part 46 Subpart B. Section 11.2 describes the additional protections for prisoners found under 45 CFR Part 46 Subpart C.

11.1 Pregnant Women, Human Fetuses and Neonates

Subpart B provides additional protections for pregnant women, human fetuses, and neonates. However, the exemptions under 45 CFR § 46.104 may apply to research involving these vulnerable populations when there is no more than minimal risk. In general, research should not routinely exclude women, who are or may be pregnant. This reduces the research’s generalizability. In other research protocols, a PI may be required to use pregnancy or the potential for pregnancy as exclusionary criteria. The IRB complies with the requirements found in 45 CFR § 46.204, which allow research on pregnant women or fetuses if all of the following conditions are met:

  1. Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;
  2. The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;
  3. Any risk is the least possible for achieving the objectives of the research;
  4. If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, her consent is obtained in accord with the informed consent provisions of the Common Rule. Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;
  5. If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the informed consent provisions of the Common Rule, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest. Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;
  6. For children as defined in 45 CFR § 46.402(a) who are pregnant, assent and permission are obtained in accord with the provisions of subpart D of 45 CFR Part 46;
  7. No inducements, monetary or otherwise, will be offered to terminate a pregnancy;
  8. Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and
  9. Individuals engaged in the research will have no part in determining the viability of a neonate.

Some studies may involve pregnant women as a part of the general population. For example, the study team recruits the potential participants from a population that includes women with childbearing potential. In these circumstances, the IRB will consider the following:

  1. Whether participants should be advised of the risks of participating in the study if they are or become pregnant;
  2. Whether pregnant women will be excluded from participation;
  3. If participants should be advised to notify the PI immediately should they become pregnant;
  4. If the subject's participation will be discontinued should the participant become pregnant;
  5. Whether participants should be advised to avoid pregnancy or nursing during or following their participation in the study;
  6. Whether pregnancy testing is required as part of the study, and if so, who bears the cost of that testing; or
  7. Whether specified methods of contraception should be required during or following participation in the research and if so, who bears the cost of such contraception?

In general, the IRB should require that the PI minimize and fully disclose the risks that may occur to women and fetuses incidentally involved in research.

11.1.1 Neonates

Neonates of uncertain viability and nonviable neonates may be involved in research if all of the following conditions are met:

  1. Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates;
  2. Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the neonate;
  3. Individuals engaged in the research will have no part in determining the viability of a neonate;
  4. As applicable for a neonate of uncertain viability, the IRB determines that: the research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or the purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means and there will be no added risk to the neonate resulting from the research. If one of these two conditions is met, then legally effective informed consent from either parent of the neonate must be obtained. If neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent's legally authorized representative is obtained. The researcher must follow the rules of the IRB's Informed Consent policy, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest; and
  5. As applicable for nonviable neonates, a nonviable neonate may not be involved in research unless all of the following additional conditions are met: vital functions of the neonate will not be artificially maintained; the research will not terminate the heartbeat or respiration of the neonate; there will be no added risk to the neonate resulting from the research; the purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and the legally effective informed consent of both parents of the neonate is obtained in accord with the WSU IRB Informed Consent Policy, except that the provisions within that policy related to waiving informed consent requirements and waiving the requirement for signed consents do not apply. However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice to meet the requirements, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest. The consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice to meet these requirements about research on nonviable neonates.

The study may include a neonate that has been determined to be viable only to the extent permitted by and in accordance with protections in Subpart D.

In addition to the Common Rule and FDA, there may be other laws regulating the research and the use of the placenta, dead fetus, macerated fetal material, cells, tissue, or organs excised from a dead fetus. The PI is responsible for identifying and informing the IRB of these laws in the research protocol. If the research record links the fetus, fetal material, or placenta to a living person in a way that allows for the identification of a person, then that living person must consent to the research study; and all other University IRB policies on human subject research apply.

11.1.2 Blood Draws on Pregnant Women and Neonates

The convened IRB must review all studies that include the following:

  1. A collection of blood samples by finger-stick, heel-stick, ear-stick, or venipuncture from pregnant adult women and children; and
  2. Where the collection of blood samples exceeds the lesser of fifty (50) ml or three (3) ml per kg in an eight (8) week period; or
  3. Where the collection of blood samples occurs more frequently than two (2) times per week.

IRB reviewers may review studies under expedited procedures, which do not fall under the aforementioned criteria.

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11.2 Prisoner Research

Prisoners may be under constraints due to their incarceration that could affect their ability to make truly voluntary and un-coerced decisions about whether or not to participate as subjects in research. Accordingly, researchers must adhere to additional safeguards for the protection of prisoners. The exemptions under 45 CFR § 46.104 do not apply to prisoners except for research aimed at involving a broader subject population that only incidentally includes prisoners. With respect to research involving prisoners, the IRB will also meet the following specific requirements in addition to the duties outlined in 45 CFR § 46.107:

  1. A majority of the IRB (exclusive of prison members) will have no association with the prison(s) involved, apart from their membership on the Board (see 45 CFR § 46.304(a)); and
  2. At least one member of the IRB will be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one Board, only one Board need satisfy this requirement (see 45 CFR § 46.304(b)).

In its Prisoner Involvement in Research (2003) Guidance, OHRP recommends that the IRB maintain “the curriculum vitae of the prisoner or prisoner representative serving on the IRB” (see Guidance Prisoner Research). The IRB will comply with this recommendation to the extent the prisoner or prisoner representative has an accessible curriculum vitae.

The University will certify to the Secretary (through OHRP) that the IRB has made the seven findings required under 45 CFR § 46.305(a). This includes the finding that the proposed research represents one of the permissible categories of research under 45 CFR § 46.306(a)(2). The University will send OHRP a certification letter, to that effect, which will include the name and address of the institution and specific identification of the research protocol, including the relevant grant number. The seven findings under 45 CFR § 46.305(a) include:

  1. The research under review represents one of the categories of research permissible under 45 CFR § 46.306(a)(2);
  2. Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;
  3. The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers;
  4. Procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the Board justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;
  5. The information is presented in language which is understandable to the subject population;
  6. Adequate assurance exists that parole boards will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and
  7. Where the Board finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners' sentences, and for informing participants of this fact.

The IRB may approve studies involving prisoners if such studies fall under one or more of the four allowable categories described in federal regulations (45 CPR § 46.306(a)(2)). It is not sufficient that the research just include one of these items, but include other items that fall outside the scope of these allowable categories. The study must only be limited in scope to research in one or more of these categories. PIs must review these categories closely and indicate to the IRB the type of category they believe their research falls under. The four categories of research are:

  1. Study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;
  2. Study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;
  3. Research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults) provided that the study may proceed only after the Secretary has consulted with appropriate experts including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of his intent to approve such research; or
  4. Research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the subject. In cases in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to control groups which may not benefit from the research, the study may proceed only after the Secretary has consulted with appropriate experts, including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of the intent to approve such research.

Effective in June 20, 2003, the Secretary of HHS received a waiver to allow HHS to conduct or support certain epidemiologic studies in which the purposes are as follows:

  1. To describe the prevalence or incidence of a disease by identifying all cases; and
  2. To study potential risk factor associations for a disease.

For most such studies, the IRB may determine that the research at issue involves no more than minimal risk and no more than inconvenience to the subjects. The human participants in this type of public health research may include prisoners in the study population. State health agencies are most commonly the conduits for this type of research.

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12. Ensuring the IRB reviews research involving children as subjects in accordance with applicable regulations

Section 12.1 defines terms “children” and “minor” based on Utah law and describes the protections for this class of research participants. Section 12.2 discusses parental and guardian consent and minor assent. Section 12.3 outlines the special requirements to conduct research on children who are wards of the state. Section 12.4 concludes with a description of the duty to report child abuse.

12.1 Children Definition

Title 45 Subpart D and Title 21 Subpart D provide special protections to children involved in research. Children are defined in 45 CFR § 46.402(a) as "persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted." Instead of using the term children, Utah uses the terms minor and child to describe a person who has not attained the legal age for consent. In the state of Utah, the terms of minor and child include any person under the age of eighteen (18) unless the following occurs:

  1. The minor is at least sixteen (16) and has been emancipated by court order (UCA § 78A-6-801 et al.);
    The minor is emancipated through marriage (UCA § 15-2-1); or
  2. The minor is emancipated by enlisting in the military (UCA § 78B-12-102(7)(a)).

The research team must seek consent from an emancipated minor rather than assent. The other special protections in Subpart D of Title 21 and 45 do not apply to an emancipated minor. The PI must include any court documents related to the emancipation of research participants under the age of eighteen (18) with their research protocols.

The Common Rule and FDA regulations permit research with children in the following instances, if the research team maintains adequate provisions for soliciting the assent of the children and the permission of parents or guardians as outlined in Section 12.2:

  1. The IRB finds that no more than minimal risk to children is presented by an intervention or procedure.
  2. The IRB finds that the study holds more than minimal risk but holds out the prospect of direct benefit for the individual subject, or by a monitoring procedure that is likely to contribute to the subject's well-being, if the IRB finds the risk is justified by the anticipated benefit to the subjects; and the relation of the anticipated benefit to the risk must be at least as favorable to the subjects as that presented by available alternative approaches.
  3. The IRB finds that more than minimal risk to children is presented by an intervention or procedure that does not hold out the prospect of direct benefit for the individual subject, or by a monitoring procedure which is not likely to contribute to the well­ being of the subject, only if the IRB finds that:
    1. i. the risk represents a minor increase over minimal risk;
    2. ii. the intervention or procedure presents experiences that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations; and
    3. iii. the intervention or procedure is likely to yield generalizable knowledge about the subjects' disorder or condition which is of vital importance for understanding or amelioration of the subjects' disorder or condition; and
  4. In rare instances, research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children may be proposed by a researcher. If the study is not funded by a federal agency, and the IRB finds and documents that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children then the IRB may approve it upon consultation with the vice president for institutional effectiveness. If the study is funded by a federal agency, and the IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children; it will be forwarded to the Secretary of Health and Human Services (DHHS) for further review.
  5. For studies involving FDA- regulated products (see Title 21 Subpart D), clinical investigations not otherwise approvable that present an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children may proceed only if the IRB finds and documents that the clinical investigation presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children; and the Commissioner of Food and Drugs, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine education, law) and following opportunity for public review and comment, determines either: (1) that the clinical investigation in fact satisfies the conditions noted above 1-3 or (2) that the following conditions are met:
    1. i. the clinical investigation presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;
    2. ii. the clinical investigation will be conducted in accordance with sound ethical principles; and
    3. iii. adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians as set forth below.

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12.2 Parental/Guardian Consent and for Assent by Children

The IRB will require that adequate provisions are made for soliciting the permission of each child's parents or guardians prior to the solicitation of the child’s assent. The IRB may find that the permission of one parent is sufficient:

  1. If the research does not involve greater than minimal risk; or
  2. If the research involves greater than minimal risk, but presents the prospect of direct benefit to the individual subjects.

If the research involves greater than minimal risk and no prospect of direct benefit to individual subjects, but is likely to yield generalizing knowledge about the subject's disorder or condition, the IRB will require both parents' permission. Exceptions would include the following situations:

  1. One parent is deceased, unknown, incompetent, or not reasonably available, or
  2. When one parent has legal responsibility for the care and custody of the child.

The research team will document parental or guardian consent in accordance with the requirements of the Common Rule and the FDA regulations. There are a few circumstances where the IRB may grant a waiver of parental consent for participation of a child in accordance with 45 CFR § 46.116. When a research protocol involves conditions or a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children), IRB may waive the consent requirements. In place of the parental or guardian consent, the IRB should ensure the following:

  1. Appropriate mechanism for protecting the children, who will participate as subjects in the research, is substituted; and
  2. The waiver in parental consent complies with federal, state, or local law.

The choice of an appropriate mechanism in lieu of parental consent would depend upon the following:

  1. The nature and purpose of the activities described in the protocol;
  2. The anticipated risks and benefits to the children participating in the study; and
  3. The children’s age, maturity, status, and condition.

The IRB will determine whether the PI has devised adequate provisions for soliciting the assent of the children when the children are reasonably capable of providing assent as determined by the IRB. In determining whether children are capable of assenting, the IRB will take into account the children’s ages, maturity, and psychological state. The IRB may make this determination based on the generalized population of children targeted for the study or on an individualized basis for each child. The assent of the children is not a necessary condition for proceeding with the research if the IRB determines the following:

  1. The capability of some or all of the children is so limited that they cannot reasonably be consulted; or
  2. The intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research.

When the IRB determines that assent is required, it will also determine whether and how the research team must document the assent.

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12.3 Wards of the State

A PI may conduct research on children, who are wards of the state, under 45 CFR § 46.404 or 45 CFR § 46.405 under the same conditions for other children. However, a PI may only include children, who are wards of the state, in research under 45 CFR § 46.406 or 45 CFR § 46.407:

  1. If such research is related to their status as wards; or
  2. If such research is conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards.

If the IRB approves such research, it will require the appointment of an advocate for each child who is a ward, in addition to any other individual acting on behalf of the child as guardian or in loco parentis. One individual may serve as an advocate for more than one child. The advocate must have the necessary background and experience. The advocate must agrees to act in the best interests of the child for the duration of the child's participation in the research. This advocate must not be associated in any way with the research, the study team, or the guardian organization.

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12.4 Child Abuse Reporting

The State of Utah requires the reporting of suspected child abuse or neglect (UCA § 62A-4a-403). This obligation to report child abuse occurs where any individual (other than clergy in a confessional) has reason to believe or has observed abuse or neglect. If the protocol involves interviewing children about topics that may lead to the knowledge or suspicion of child abuse or neglect, the study team must inform the child and, where appropriate, the parent/guardian of the reporting requirement as part of the informed consent process. The team should make reports of child abuse to the Utah Division of Child and Family Services, or its equivalent in the jurisdiction where the research study team conducts the research.

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13. Reviewing the qualifications of the investigator(s) and study staff, and the adequacy of the site where the research will be conducted

The University IRB requires training for all faculty, faculty mentors, researchers, and students. This includes researchers from other institutions who wish to conduct human subject research at the University. All key personnel (PI, Co-PI, Faculty Sponsor)—originally listed in the protocol or later added to a study through an amendment—must complete the required human subject training. In order to comply with the policy, the IRB requires all key personnel to complete the CITI Program modules as specified by the IRB Chair. Key personnel in research must complete this training every three (3) years. The IRB reviewers will check protocol submissions (initial, continuing, amendments) to assure all researchers and research staff have completed the training. The IRB will not approve protocol actions until the key personnel listed on the protocol complete this training. The University may make webinars and local conferences available to the University community for additional training.

Any site selected for research must adequately promote the validity of the research findings and mitigate the risk of the research participants. The IRB may require the PI to provide a justification for a site selection if the site may impair the validity of the research findings. The IRB may require the PI to provide written justifications for this site selection if it presents risks to research participants. The PI is encouraged to mitigate risks where possible and not poise additional risks to research participants based on the research site selection.

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14. Assessing and managing investigator conflict of interest, if any

All PIs and their research staff are required to disclose any conflict of interest including any financial conflict of interest. The research team must comply with University PPM 3-36 which governs University conflict of interest. Disclosed conflicts of interest that might affect the protection of subjects must have a management plan in place. Management plans may include:

  1. Partial or complete divestment;
  2. Limiting involvement of the conflicted individual;
  3. Additional oversight; and
  4. Full disclosure of current and potential conflicts of interest.

The research team’s disclosure of a conflict of interest is not sufficient to manage conflicts of interests that might affect the protection of subjects. PIs will be responsible for devising such a management plan and receiving signed authorization from their supervisor and the review of University General Counsel’s Office. When finalized, the PI will submit the conflict of interest management plan to the IRB for review and final approval. The IRB must first review and approve the conflict of interest management plan before the IRB can approve the research protocol.

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15. Determining the applicability of state and local laws

The IRB has the responsibility to protect the rights and welfare of human research subjects. The IRB reviews and oversees research activities involving human subjects and requires that the research complies, as applicable, with Federal regulations at 45 CFR Part 46, Subparts A, B, C, and D, (or equivalent policies and procedures), the FDA 21 CFR Parts 50, 56, 312, and 812. To the extent PI may engage in research activities which are governed by other federal, state and municipal laws, the PI has the obligation to use his/her reasonable best efforts to identify such laws and consult with University General Counsel’s Office. IRB may provide non-legal guidance on obligations and duties to the PI. However, the PI has the responsibility to ensure that his/her proposed research does not violate any federal, state, or municipal law.

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16. Determining and documenting the effective date of initial approval, and calculating the date for subsequent continuing review

The date of the initial approval (Effective Date) is the date at which the IRB reviewer dated the approval letter. The continuing review date is one of the following:

  1. The date specified in the approval letter; or
  2. The date three hundred and sixty-four (364) days from the Effective Date.

After July 19, 2018, in accordance with 45 CFR § 109(f), the Common Rule no longer requires continuing review, unless the IRB expressly determines otherwise in the approval letter, in the following circumstances:

  1. The research is eligible for expedited review under 45 CFR § 46.110;
  2. The IRB reviewed the research in accordance with the limited reviewed described in 45 CFR § 46.104(d)(2)(iii); or
  3. The research has progressed to the point that it involves only one or both of the following, which are part of the IRB approved study: (A) Data analysis, including analysis of identifiable private information; or (B) Accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care.

For full board research or expedited research with a continuing review requirement, the PI has the responsibility to send the IRB a completed continuing review form prior to:

  1. The date specified in the approval letter; or
  2. If not expressly mentioned in the approval letter, before three hundred and sixty-four (364) days if they are still actively collecting data as part of the research.

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17. IRB member attendance required to conduct a convened meeting

Section 17.1 begins with an overview of when an IRB meeting is convened. Section 17.2 outlines the number of members on the IRB, how an IRB quorum is defined and maintained, and the process the IRB follows if the quorum is lost during a meeting. Section 17.3 describes the prohibition of proxy votes. Section 17.4 provides an overview of managing any IRB member or alternate member conflict of interest.

17.1 Convened Meeting

As required by 45 CFR § 46.108(b) and consistent with Part 3, a convened IRB meeting occurs when:

  1. A majority of the members of the IRB are present; and
  2. At least one member whose primary concerns are in nonscientific areas is present.

At the discretion of the IRB Chair and the vote of the majority IRB committee members, the IRB may appoint alternate reviewers to stand in the place of the IRB committee members consistent with Section 3.4 of these Written Procedures.

17.1.1 Electronic Meetings

Consistent with the “IRB Meetings Convened via Telephone Conference Call: OPRR Memorandum (2000)”, IRB committee members may participate remotely in and be counted towards a majority for a convened IRB meeting through electronic means so long as the following occurs:

  1. Each participating IRB member “has received all the pertinent material prior to the meeting”; and
  2. These members “can actively and equally participate in the discussion of the protocols.”

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17.2 Number of IRB Members and Quorum

In accordance with 45 CFR § 46.107, the University will maintain at least five IRB members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB will appoint members to safeguard the rights and welfare of human subjects in accordance with the following criteria:

  1. The members are sufficiently qualified through their experience and expertise;
  2. The members are diverse including a diversity in race, gender, and cultural backgrounds; and
  3. The members are sensitive to such issues as community attitudes.
17.2.1 Quorum

To determine whether the majority of the IRB members are present, first the total number of IRB members present including alternates replacing primary reviewers will comprise the numerator. The total number of the primary reviewers comprise the numerator. The denominator then divides the numerator (e.g. IRB Members Present ÷ Total Number of Primary Reviewers). Accordingly, a majority of the IRB members are present when one the following occurs:

  1. More than fifty percent of the total primary reviewers are present at the IRB meeting; or
  2. The primary reviewers and one or more alternate reviewers, acting on behalf of the primary reviewers, are present at the IRB meeting and comprise more than fifty percent of the total primary reviewers.

For the IRB to approve a protocol, the majority of the IRB members present must receive approve the protocol (see 45 CFR § 46.108(b)). During the course of a convened IRB meeting, the IRB may not take any official action including the approval of research without a quorum.

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17.3 Prohibition on Proxy Votes

The IRB does not allow any proxy votes in any form although alternates may vote as proscribed in Section 3.4.

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17.4 Conflict of Interest

No member of the IRB may participate in the review and approval process for any human research in which he/she has an actual or potential conflict of interest. Any IRB member or alternate—whose name appears anywhere in the research application or who has any reason to believe that he/she will have a role in the research—must disclose their conflict. The IRB will excuse any IRB members, who have conflicts of interest, from the meeting. Any IRB member or alternate who feels he/she might not be completely objective in doing the review for any reason may excuse himself/herself. Where the PI member has a conflicting interest, he/she must leave the meeting room during the voting phases of the review and approval process. Any member, excused for purposes of conflicts of interest or objectivity, will not count towards the quorum requirements. The IRB minutes will reflect the exclusions based on conflicts of interest and other matters.

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18. Communicating the IRB’s findings and actions, and any decision to approve or disapprove the proposed research activity or of modifications required to secure approval of the proposed research activity in writing to the investigator and the institution

Section 18.1 begins with a description of the written information the IRB provides to the PI regarding its findings and actions (e.g., approve, require modification in to secure approval, disapprove). Section 18.2 describes to whom the IRB notifies of its findings and actions. Section 18.3 outlines how the IRB communicates notifications to the PI and the University, including the associated timelines for such notifications. Section 18.4 describes how the IRB communicates modifications or clarifications required by the IRB in writing to the PI. Section 18.5 outlines how the IRB subsequently reviews and acts upon the PI’s response to any required modifications or clarifications, and the associated timelines for the PI’s response. Section 18.6 concludes with an overview of how the IRB communicates the reasons for a decision to disapprove, and the process followed to allow the PI to respond.

18.1 Written Information

The IRB will make written determinations to approve research. In these written determinations, the IRB will communicate the reasons for the approval to the PI. An approval letter requires no further action, and the PI can begin research. However, IRB reviewers or the IRB committee may communicate via email or other written forms when a research requires modifications to receive approval. For tabled protocols, the IRB will notify the PI in writing about why the IRB tabled the protocol. These communications may occur via email or other written means. The PI must revise and resubmit the entire protocol, with all supporting documents, as needed. The IRB committee will write a disapproval letter with the reasons for the disapproval. This letter must specify how a PI may respond in writing or in person to the disapproval of the research protocol.

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18.2 Notification

In full board research, generally the IRB will directly notify the PIs. The IRB may also apprise the Institutional Official of a research protocol, which the IRB considers to have high risk. The IRB will notify all IRB members of research reviewed under the expedited process by providing these members access to expedited research stored in the centralized record repository.

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18.3 Communication Means and Timelines

The IRB must communicate approvals and disapprovals through written communications with statements describing the reasons for these decisions. The IRB may communicate modifications in order to secure approvals or tabled determinations by email or other written means to facilitate the communication between the parties.

In terms of timelines, IRB reviewers will use their reasonable efforts to provide a written decision within ten (10) business days of a decision. These timelines are aspirational. A high volume of IRB submissions or other competing interests may delay the response time.

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18.4 Modifications Communicated

To expedite the review process, IRB reviewers and the IRB committee may communicate modifications to PIs via email or through other electronic means. Written communications giving approval with explicit conditions will contain a list of required conditions. Until all these PI meets all the required conditions, the IRB will not provide the final approval.

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18.5 Approval of Modifications

To approve research in which the IRB has required modifications, the IRB will determine whether the PI’s responses to the conditions will require additional IRB review for appropriateness and completeness. This review may include:

  1. A review at another IRB convened meeting;
  2. A review by the IRB Chair, or
  3. A review by a designated reviewer.

This determination may occur at the time the IRB makes the determination that the proposal requires modifications. The PI must timely provide the required modifications to the research protocol. Upon a delayed response by the PI, the IRB may require that the research protocol undergo another full board review or expedited review. When the PI has responded to all conditions appropriately and completely, then the PI may grant the final approval. The IRB will notify the PI by an approval letter that the research can begin. This approval letter will indicate whether and when the protocol will require continuing review.

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18.6 Disapproval

The IRB committee will write a disapproval letter with the reasons for the disapproval. This letter must specify how a PI may respond in writing or in person to the disapproval of the research protocol. Accordingly, a PI may request reconsideration of disapproved studies by submitting a written response to the IRB. The IRB may invite the PI to the IRB meeting if the IRB has additional questions. The IRB may reconsider its original decision in light of new information presented by the PI.

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19. Tracking study approvals and scheduling continuing review to prevent lapses in IRB approval, including procedures to be followed if there is a lapse in IRB approval

19.1 Continuing Review

The IRB has the responsibility to ensure that the research team conducts research in accordance with the law and IRB requirements. Accordingly, the IRB will conduct continuing review of approved research not less than once a year. However, after July 19, 2019, continuing review is not required for research within the following categories:

  1. Research eligible for expedited review under 45 CFR § 46.110;
  2. Research reviewed by the IRB in accordance with the limited reviewed described in 45 CFR § 46.104(d)(2)(iii); or
  3. Research that has progressed to the point that it involves only one or both of the following, which are part of the IRB approved study: (A) Data analysis, including analysis of identifiable private information; or (B) Accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care.

When approving the study, the IRB (or IRB Chair or his/her designee in the case of an expedited review) will determine if the risks are of a sufficient magnitude that the IRB should require continuing review more often than annually. When determining whether a study requires continuing review more frequently than once a year, the IRB will consider the following factors:

  1. Studies that involve experimental therapies or procedures in which a clear potential for significant adverse experiences has been identified at the time of review;
  2. The nature, probability and magnitude of anticipated risks to subjects;
  3. The medical, psychological, or physical conditions of the proposed subjects, age of subjects;
  4. The qualifications and experience of the PI and other members of the research team;
  5. The nature and frequency of adverse events observed in similar research;
  6. The IRB’s previous experience with the investigator and/or sponsor;
  7. The projected rate of enrollment;
  8. The vulnerability of the population being studied including familiarity with the language on consent forms and other documents; and
  9. Other facts the IRB deems relevant to the nature of the study and risks posed by the study.

A PI, who desires to continue doing research on a study that requires continuing review, must submit the continuation review form. This must occur before a lapse in approval for the research. The IRB recommends that a PI submit for continuing review at least two (2) months prior to the continuing review date. Federal regulations and University policy do not allow for any form of grace period. The research may not begin again until the IRB approves the study for another continuing review period. The IRB will conduct the continuing review at the appropriate level based on the risk. Typically, IRB will review studies at the same level for continuing review as for initial review. For this reason, the PI will submit the following:

  1. A completed continuing review form;
  2. A copy of the current informed consent and any newly proposed consent document; and
  3. One copy of the complete protocol including any modifications previously approved by the IRB if his/her study was originally reviewed by the full board.

In some instances, the IRB may conduct continuing review of full reviewed protocols at the expedited level. The IRB Chair will make such determinations in keeping with the expedited categories enumerated by the OHRP and FDA. For studies involving FDA regulated products, if there is a sponsor protocol and/or clinical investigator brochure, then the PI must submit copies of these documents to the IRB.

During the continuing review, the IRB should focus on whether there is any new information about the research, provided by the PI or other sources, which would alter the IRB’s previous determinations. More particularly, the IRB should first consider the research’s benefits and risks to the subjects by evaluating whether:

  1. The risks to subjects are minimized,
  2. The risks to subjects are reasonable in relation to anticipated benefits, if any, to the subjects; and
  3. The risks are reasonable in relation to the importance of the knowledge that may reasonably be expected to result (45 CFR 46.111(a)(1) and (2); see also Continuing Review Guidance (2010)

Second, the IRB should review the most up-to-date informed consent document. The IRB will ensure that the informed consent document complies with the requirements of the informed consent under the Common Rule or the FDA regulations. The IRB should consider whether the informed consent document adequately informs potential research participants of the following:

  1. The reasonably foreseeable risks and discomforts of the research; and
  2. Any appropriate alternative procedures or courses of treatment that might be advantageous to the research participants.

The IRB also should evaluate whether there is any new information that indicates the informed consent procedures are inadequate to secure lawful consent.

Third, as applicable, the IRB should consider investigator and institutional issues including:

  1. Changes in the PI’s situation, licensure, qualifications, and research activity;
  2. Evaluation, investigation, and resolution of any complaints related to the PI’s research;
  3. Changes in the acceptability of the proposed research in terms of institutional commitments (e.g., personnel and financial resources, adequacy of facilities) and applicable regulations, state and local law, or standards of professional conduct or practice; and
  4. Reports from any third-party observations of the research.

Fourth, the IRB should evaluate the research progress including:

  1. Whether the current research conforms with the research presented in the original protocol;
  2. Whether the actual subject enrollment is consistent with the proposed enrollment; and whether any inconsistency may impact the scientific validity of the research or indicate other problems; and
  3. Whether the research has a relatively high rate of participant withdrawals and whether this indicates problems with the research.

Once the IRB makes a decision, the IRB Chair or his/her designee will notify the PI with a copy to the IRB Compliance Officer. Additionally, in the case of student investigators, faculty sponsors are also included in the electronic communication. The IRB maintains all records of continuing review within the respective protocol's file housed at the data repository. For continuing review conducted at convened meetings, the minutes will reflect any discussions related to the continuing review process and list the items submitted for review by the PI or his/her staff.

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20. For FDA-regulated research, reviewing the emergency use of a test article

The University does not have a medical school or an affiliated hospital. Consequently, it does not perform clinical trials in which emergency use would likely occur. To qualify for the emergency use of test article exemption (see 21 CFR § 56.104(c)), the PI needs to demonstrate the following in written documentation:

  1. The use of a test article on a human subject was in a life-threatening situation in which no standard acceptable treatment was available, and in which there was not sufficient time to obtain IRB approval (see 21 CFR § 56.102(d));
  2. There was no previous use of the test article (see 21 CFR § 56.104(c)); and
  3. The emergency use was reported to the IRB within five (5) working days (see 21 CFR § 56.104(c)).

The PI needs to submit this written documentation to the designated IRB reviewer. Then the designated IRB reviewer will store this written documentation in the designated repository. The IRB may waive obtaining informed consent according to 21 CFR § 50.23. This may occur so long as both the PI and a physician, who is not otherwise participating in the clinical investigation, certify in writing all of the following:

  1. The subject is in a life-threatening situation necessitating use of test article;
  2. The consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the subject;
  3. There is not sufficient time to obtain consent from subject's legal representative; and
  4. There is no alternative method of approved or generally recognized therapy that provides an equal or greater likelihood of saving the life of the subject.

Absent a certification from a physician, this waiver may also occur when:

  1. The immediate use of the test article is required to save the life of the subject;
  2. There is not enough time to obtain an independent determination by another physician before using the test article;
  3. Within five (5) business days, a physician, who is not participating in the study, will review and evaluate the PI’s determination; and
  4. The PI submits the documentation, required for the exception under FDA regulations, to the IRB within five (5) working days after the use of the test article.

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21. For FDA-regulated research, reviewing a request for expanded access or treatment use

Given the nature of the research at the University and fact that it does not have an affiliated hospital, it is unlikely that the University will have occasion to review a request for expanded access or treatment use. To the extent that the IRB reviews a request for expanded access or treatment use, the IRB will ensure that the following requirements occur:

  1. The patient and a licensed physician are both willing to participate;
  2. The patient's physician determines that there is no comparable or satisfactory therapy available to diagnose, monitor, or treat the patient’s disease or condition;
  3. That the probable risk to the person from the investigational product is not greater than the probable risk from the disease or condition;
  4. FDA determines that there is sufficient evidence of the safety and effectiveness of the investigational product to support its use in the particular circumstance;
  5. FDA determines that providing the investigational product will not interfere with the initiation, conduct, or completion of clinical investigations to support marketing approval;
  6. The sponsor (generally the company developing the investigational product for commercial use) or the clinical PI (or the patient’s physician in the case of a single patient expanded access request) submits a clinical protocol (a document that describes the treatment plan for the patient) that is consistent with FDA’s statute and applicable regulations for INDs or investigational device exemption applications (IDEs), describing the use of the investigational product; and
  7. The patient is unable to obtain the investigational drug under another IND or to participate in a clinical trial.

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22. For FDA-regulated research, reviewing a request for the use of a Humanitarian Use Device (HUD)

Given the nature of the research at the University, it is unlikely that research will employ a Humanitarian Use Device (HUD). To the extent that the University may apply for a HUD, the IRB and researchers will rely upon “Guidance for Industry and Food and Drug Administration Staff Humanitarian Use Device (HUD)” for its policies and procedures (see Guidance for HUD)

Designations In accordance with 21 CFR § 814.3(n), and as amended by the 21st Century Cures Act, a HUD is a “medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year.” PIs will notify the IRB Chair and IRB Compliance Officer of his/her intention to apply for a HUD designation. Prior to submitting any materials to the FDA to obtain an HUD, the PI is required to submit all such materials to the IRB Chair. According to the FDA, the PI must submit the following materials to obtain a HUD:

  1. Sufficient documentation, with appended authoritative references, to demonstrate that the device meets this HUD definition;
  2. The proposed indications for use of the device; and
  3. The reasons why such a device is needed for the patient population.

One aspect that has become increasingly difficult is if the PI applies for HUD for an indication that represents a subset of a common disease or condition. In these situations, the applicant must demonstrate that the subset is an “orphan subset.”

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23. For FDA-regulated in vitro diagnostic (IVD) research, IRB considerations of the use of leftover specimens without informed consent, when the specimens used for IVD development are not individually identifiable

In vitro diagnostic devices (IVDs) are products (reagents, instruments, and systems) intended for use in the diagnosis of disease or other conditions. These diagnoses may involve the determination of the state of patient’s health to cure, mitigate, treat, or prevent a disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body (21 CFR § 809.3). The FDA considers IVDs to be devices and consequently regulates them. In many cases, the research usually involves the comparison of the IVD under investigation to the “gold standard” using data generated from samples analyzed on both instruments. The PI must submit the comparison data and subsequent statistical analysis to the FDA for consideration of clearance or approval for marketing.

The FDA regulations do not distinguish between IVDs and implanted devices regarding informed consent. However, IVD studies often involve laboratory samples already analyzed for clinical and/or diagnostic reasons. As a result, the research team may encounter difficulty obtaining informed consent to use the samples for IVD analyses. The FDA authored a guidance document entitled “Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable Guidance for Sponsors, Institutional Review Boards, and Food and Drug Administration Staff” (see Guidance for IVD https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071265.pdf). In this document, the FDA outlines the criteria under which the FDA does not require consent for the use of “leftover specimens” in IVD studies. These criteria include:

  1. The investigation meets the IDE exemption criteria at 21 CFR § 812(c)(3);
  2. The study uses leftover specimens collected for routine clinical care or analysis and/or leftover specimens that were previously collected for research purposes;
  3. The specimens are not individually identifiable;
  4. The specimens may be accompanied by clinical information as long as the information does not make the specimen source identifiable to the PI or any other person associated with the investigation;
  5. The individuals caring for the patients are different from and do not share information about the patient with those conducting the study;
  6. The specimens are provided to the PI without identifiers and the supplier has established procedures to prevent the release of personal information; and
  7. The IRB has reviewed and approved the study has been reviewed.

The FDA has a guidance document entitled “Guidance for Industry and FDA Staff In Vitro Diagnostic (IVD) Device Studies -Frequently Asked Questions" which the PI should review before proposing IVD studies (see Guidance IVD). The IRB may review proposed research on IVDs using an expedited review process so long as the research meets all the expedited criteria and one of the expedited categories of research.

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24. Handling subject complaints, problems, concerns and questions about rights as a research subject

IRB and other members of the University must address any complaints from research participants. Based on the facts of the complaints, the IRB may make resolutions, which protect the rights and welfare of research participants. A research participant or his/her representative may voice a concern or complaint. When addressing participant complaints, the University must maintain appropriate privacy and confidentiality protections to ensure the protection of the participant.

If a PI or his/her study team receives a participant complaint, the PI must address and resolve the complaint in a manner, which protects the participant’s rights and complies with the IRB-approved study. The PI must report to the IRB in the following ways:

  1. If the complaint meets the definition of an unanticipated problem, the PI must report the complaint promptly to the IRB. The PI may not completely resolve the complaint prior to the prompt reporting deadline. However, the PI must still report the complaint promptly. In this report, the PI should describe the status of the complaint resolution and his/her plan to resolve the complaint. If the complaint involves possible non-compliance or research misconduct, the IRB and University will review the complaint according to IRB and University policy;
  2. If the PI is unable to resolve the complaint satisfactorily with the participant, the PI must report the complaint to the IRB as soon as the PI determines that he/she cannot resolve the problem without additional help from the University.
  3. If the complaint does not meet either of the two criteria above, the PI must report the complaint at the next continuing review. The PI must provide the following:
    1. i. A short summary of the complaint;
    2. ii. How the PI resolved the complaint; and
    3. iii. Why the complaint did not meet criteria for prompt reporting as an unanticipated problem.
  4. If the complaint results in the need to change the IRB approved study, the PI must also submit an amendment to the IRB so the IRB can begin the review of the amendment.

If the IRB receives a participant complaint, the IRB will take the necessary steps to address the complaint. If the complaint identifies a specific study of concern, the IRB will contact the PI of the study to help address the complaint. The PI will then document the receipt of the complaint as well as the process used to address the complaint in collaboration with the IRB. The IRB will review these reports according to the unanticipated problem and/or non-compliance policies, as appropriate.

If any University member other than IRB or the study team receives the participant complaint, this member must contact the IRB Chair to report the complaint. The IRB will then follow the aforementioned procedures to address the complaint.

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25. Implementing cooperative IRB review arrangements

The IRB will have special responsibilities in the review and approval of proposals involving cooperative activities. Cooperative research activities involve either instances where:

  1. The University faculty, students or staff, obtain access to human subjects involved through one or more cooperating institutions, or
  2. The PIs from cooperating institutions obtain access to human subjects at the University.

The IRB will comply with the requirements of 45 CFR § 46.114 to rely upon the approval by a single IRB for the portion of the research conducted in the US. In order to enable this reliance on a single IRB, the University will enter into IRB authorization agreements, which the IRB Compliance Officer will review. The Institutional Official, which is currently the Provost, will sign these agreements. When the IRB approval occurs at another entity, the PI will provide the IRB a copy of the approved research protocol materials and the IRB approval notification for documentation.

When a PI plans to conduct research at a site external to the University (not owned or operated by the University), the PI must provide the following information to the IRB:

  1. The contact information of the site(s);
  2. Whether the site(s) has an IRB;
  3. Whether the site(s) has granted permission for the research to be conducted; and
  4. If the site has an IRB, has the IRB approved the research or does the site plan to defer to the University IRB.

If the site defers to the IRB, the site must submit a FWA that designates the institution’s IRB as an IRB that the site relies upon for review of human subject research. The IRB Compliance Officer will communicate to the site as needed. Generally, the parties must draft and execute an IRB authorization agreement that delineates the specific roles and responsibilities of each participating institution. Activities involving investigators from one or more institutions who may exchange or pool similar data obtained from human subjects who participate in independently sponsored projects are not cooperative activities as defined above. For PIs performing research in which the University is the lead or coordinating institution, the PI should note in the initial IRB application that the University is the lead or coordinating institution of a multi-site study. The PI should also provide the following information:

  1. The name(s) of each participating institution that will be engaged in human subjects’ research;
  2. Confirmation that each participating institution has an FWA;
  3. The contact name and information for the PI at each institution;
  4. The contact name and information for the IRB of record at each institution; and
  5. The method of multilateral communication between institutions/IRBs of any unanticipated problems involving risks to subjects or others and other study related information.

The researcher should also upload copies of IRB approved documents and relevant correspondence between the participating sites.

If research has been determined to be exempt and not subject to the Common Rule, the University will not enter into an Authorization Agreement. The PI will provide the following information to IRB for documentation purposes:

  1. A copy of the IRB exempt determination; and
  2. A copy of the research protocol.

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Section II: title

26. Deciding which research studies require review more often than annually and the criteria used in the determination

Section 26.1 discusses the specific criteria used by the IRB to determine the approval period. Section 26.2 describes where the IRB documents its determination about the approval period. Section 26.3 concludes with an overview of how the IRB communicates its determinations regarding the approval period to the PI.

26.1 Specific Criteria

The IRB will determine the approval period based on the following factors:

  1. The degree to which the studies involve experimental therapies or procedures in which a clear potential for significant adverse experiences has been identified at the time of review;
  2. The nature, probability and magnitude of anticipated risks to subjects;
  3. The medical, psychological, or physical conditions of the proposed subjects;
  4. The age of the proposed subjects;
  5. The qualifications and experience of the PI and other members of the research team;
  6. The nature and frequency of adverse events observed in similar research;
  7. The IRB’s previous experience with the PI and/or sponsor;
  8. The projected rate of enrollment;
  9. The vulnerability of the population being studied including familiarity with the language on consent forms and other documents; and
  10. Other facts the IRB deems relevant to the nature of the study and risks posed by the study.

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26.2 Documentation of Approval Period

The IRB will document the approval period in the approval letter to the PI either expressly or by default three hundred and sixty-four (364) days from the approval date. The IRB will store all approval letters in the centralized data repository.

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26.3 Communication

The IRB will communicate the approval period in the approval letter to the PI either expressly in the approval letter or by default in accordance with Section 26.2.

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27. Deciding which projects need verification from sources other than the investigator (such as the sponsor, or other third party) that no material changes have occurred since previous IRB review and the criteria used in the determination

In keeping with the IRB’s responsibility to conduct ongoing monitoring of approved research, the IRB may independently inquire into the following:

  1. Whether the research is in compliance with federal and state laws and regulations and University policies;
  2. Whether the research is being conducted in accordance with approved protocols; and/or
  3. Whether the study procedures are harming research participants.

The IRB may determine that verification is necessary based on the following criteria:

  1. The extent to which material changes have occurred since the previous IRB review;
  2. The degree to which the study involves experimental therapies or procedures in which a clear potential for significant adverse experiences has been identified at the time of review;
  3. The number or character of complaints from a research participant or a third-party;
  4. The degree to which one or more of the investigators has/have an actual or apparent conflict of interest;
  5. The number or character of allegations of scientific misconduct;
  6. The nature and frequency of adverse events observed in similar research, or the nature and frequency of adverse events observed in the protocol under review, warrants concern;
  7. The extent to which the study involves a vulnerable population, including those who may be unfamiliar with the language on consent forms and other documents;
  8. Whether there is allegation that research activity is being or has been conducted with IRB approval;
  9. To the extent the IRB adopts procedures to randomly select projects for verification;
  10. The extent to which the projects are complex involving risk to subjects;
  11. The extent to which the projects are conducted by PIs who previously failed to comply with the regulations or the requirements or determinations of the IRB;
  12. To the extent that possible material changes are occurring in research without IRB approval; and
  13. To the extent that IRB believes that there are problems that exist within projects.

The IRB Chair will review the information presented from the PI as well as other sources and determine if further investigation is necessary. The IRB may verify noncompliance of the protocol using sources other than the PI and research staff without first contacting them. However, the IRB may notify the PI before the independent verification occurs. Notwithstanding the foregoing sentence, the IRB has no duty to notify the PI. The IRB Chair will present the results of the verification in a convened IRB meeting. The IRB may suspend or terminate the research. The PI may submit appeals of the decision in accordance with University PPM 4-34b. In consultation with the Institutional Official, the IRB Chair may suspend the research prior to a convened IRB meeting to protect the human subjects form imminent hazards. The IRB will notify the Pl of any additional actions.

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Section III: Ensuring Prompt Reporting to the IRB of Proposed Changes in a Research Activity, and Ensuring that Changes in Approved Research, During the Period for Which IRB Approval Has Already Been Given, May Not be Initiated Without IRB Review and Approval Except Where Necessary to Eliminate Apparent Immediate Hazards to the Human Subjects [45 CFR § 46.103(b)(4)(iii), 21 CFR § 56.108(a)(3) and (4)]

28. Informing investigators they may not implement any changes in research activities without prior IRB review and approval, except when necessary to eliminate apparent immediate hazards to subjects

Section 28.1 describes how the IRB informs a PI about not implementing changes to research without prior to the IRB review and approval. Section 28.2 outlines steps taken to ensure that the PI reports changes in research to the IRB prior to their implementation.

28.1 Notice

The PI must notify the IRB of any proposed changes in the protocol or consent forms prior to the initiation of these changes. The PI does this via an amendment form. Changes may include:

  1. Modification of protocol procedures;
  2. Modification of informed consent procedures, or
  3. Changes in data collection instruments.

The PI may not initiate these changes without IRB review and approval, except where necessary to eliminate imminent hazards. The IRB may inform a PI of this duty through approval letters and training modules such as CITI Program. This Written Procedures Manual provides constructive notice to a PI of this duty.

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28.2 Audit

The IRB and University can conduct audits of approved research to ensure compliance with IRB requirements. The University authorizes the IRB to monitor or to have a third party monitor the informed consent process or other aspects of the research protocol. Additionally, governmental agencies may also review these research records. The University may randomly audit approved studies and may elect to target particular research protocols.

Any IRB member may request an audit. The IRB Chair and the IRB Compliance Officer will review all audit requests. Once the IRB Chair or IRB Compliance Officer determines an audit to be proper, the IRB Chair will contact the PI in writing. This writing will request that the PI deliver all research records to the IRB within thirty (30) days. The PI has a duty to meet with auditors or IRB members and cooperate with them. After reviewing the research records and performing relevant interviews, the IRB Chair or his/her designee will write an audit report. Prior to submitting the audit report to the Institutional Official, the IRB Chair will solicit feedback from the PI. At the conclusion of the audit, the IRB Chair of his/her designee will prepare the final report and submit it to the Institutional Official.

The University, IRB, or governmental agencies can review studies that have ended. The PI should retain research related documents for a minimum of three (3) years from the study’s end date. In the case of federally funded research, the PI must keep these records for the time specified in the award document if longer than three (3) years. For multi-site studies, the study’s end date is the date when the sponsor closes the research or the last research site concludes the research whichever date is later. The IRB Compliance Officer will maintain all records in a reasonable manner consistent with industry practices. Informed consent documents must expressly authorize the University, the IRB, and regulatory agencies to review research records, which may contain personal or confidential information.

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29. Receiving and processing materials about changes in research

Section 29.1 describes what qualifies as a minor change in research. Section 29.2 outlines a list of documents submitted to the IRB. Section 29.3 discusses the timelines for receipt of submissions, scheduling IRB review, and document distribution. Section 29.4 provides a description of the criteria used to determine whether full board review is required or whether the changes qualify for expedited review procedures. Section 29.5 describes how the IRB determines whether the approved informed consent form requires revision.

29.1 Minor Changes

Minor changes are changes characterized by the following:

  1. The changes involve minimal risk procedures;
  2. The changes do not increase the risk or decrease the potential benefit to subjects;
  3. The changes do not involve one or more of the regulatory criteria; and/or
  4. The changes may include categories in expedited list published by the Federal Register.

Typical minor changes include, but are not limited to:

  1. Changes in the personnel;
  2. Non-significant changes in sample size;
  3. An addition of a questionnaire that does not include sensitive or controversial questions;
  4. A change in the compensation schedule, or
  5. An addition of a site, etc.

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29.2 Submission Requirements

The requirements for amendments submission are:

  1. Completed amendment application.
  2. Revised consent process described in protocol or document with the changes highlighted.
  3. Protocol, recruitment, enrollment, or other study activity or procedure if modified.
  4. Requests must describe what modifications are desired, why the changes are required, and if the changes pose any additional risks to the subjects.

A PI may only submit additional amendments after the IRB approves any prior amendment for the same protocol. If the PI submits a new protocol amendment while the IRB is still reviewing a prior amendment request for the same protocol, the IRB will not review the new amendment request.

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29.3 Timelines

The IRB will follow the timelines outlined in Parts 3 and 4 relating to the expedited and full board review process.

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29.4 Process

The IRB may approve minor changes through an expedited review process. Reviewers using the expedited review process must consider the following:

  1. Whether the amendment is a minor modification to previously approved research; and
  2. Whether the regulatory criteria for approval are met.

At his/her discretion, the reviewer may refer the amendment to the convened IRB. The IRB reports all amendments reviewed through an expedited process effectively through the deposit of these amendments in the centralized repository. All IRB members will have immediate access to this centralized repository.

The convened IRB must review all changes, which are more than minor or those that involve one or more of the regulatory criteria. When the convened IRB reviews amendments, all IRB members will have a copy of all documents the PI submitted. At the convened meeting, the IRB members will discuss and deliberate over the proposed amendment prior to voting. Any member not present for a substantial portion of the discussion and deliberations should abstain from voting.

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29.5 Informed Consent

After approval, amendments to the informed consent/assent form or protocol may require that active research participants be re-consented using the revised consent/assent forms. The IRB may waive this requirement for minor changes to the protocol or consent documents.

Minor changes to informed consent forms are limited to the following:

  1. Changes in location of the research activities;
  2. Changes to the title of the study;
  3. Formatting changes; or
  4. At the discretion of the IRB Chair or the designated reviewer, changes in the research team.

Any other changes to the consent/assent form, arising from an amendment approval, may require the re-consent of active subjects. Active subjects must always be re-consented if the following occurs:

  1. The amendment approved changes to the consent/assent form information with respect to risks or benefits of the study; or
  2. The amendment adds or removes activities from the study.

In some instances, at the discretion of the IRB Chair or the designated reviewer, amendments also may necessitate the re-consent of subjects who no longer are participating in the study. This type of amendment may include a change in the study prompted by the identification of a risk. The PI must then add to the consent/assent form and protocol information the newly identified risk.

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30. Communicating to the investigator and the institution the IRB’s decision to approve or disapprove the proposed change in research activity or of modifications required to secure approval of the proposed change in research activity

Section 30.1 describes how the IRB communicates the required conditions of approval to the PI including modifications or clarifications. Section 30.2 outlines how the IRB subsequently reviews and acts upon the PI’s responses to any required modifications or clarifications, and the associated timelines for the PI’s response. Section 30.3 discusses how the IRB communicates the reasons for a decision to disapprove the change in research activity, and the process followed to allow the PI to respond.

30.1 Modifications

The IRB full board or the expedited reviewer may communicate via email or another method of writing the modifications or clarifications required by the IRB as a condition of approval.

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30.2 Investigator Responses

To the extent that the PI disputes the modifications or clarifications, the PI must follow the appeal process in PPM 4-34b. In this process, the PI may submit in writing an appeal to the Provost and to the IRB Chair. The PI’s statement must outline the reasons for the appeal. The PI must make an appeal to the IRB within thirty (30) days of the date the PI received notification of the IRB’s decision.

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30.3 Notification

Once the IRB reviews amendment(s) to a study, the IRB Chair will notify the PI in writing of the determination. If a study is originally exempt and the amendment does not alter the criteria for exempting the study, then the IRB reviewer will notify the PI in writing that the study is exempt The IRB reviewer will store this exempt determination and documentation in the centralized document repository. If the IRB approves the amendments, then the PI may implement the approvals after the PI receives notification of the approval. A PI may implement proposed changes before approval only when necessary to eliminate imminent hazards to research subjects. If a PI disagrees with a decision, the PI may follow the process found in PPM 4-34b to appeal the decision.

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Section IV: Ensuring Prompt Reporting to the IRB, Appropriate Institutional Officials, Any Department or Agency Head, OHRP and FDA of Any Unanticipated Problems Involving Risks to Human Subjects or Others, Any Instance of Serious or Continuing Noncompliance with the Applicable HHS and/or FDA Regulations, or the Requirements or Determinations of the IRB, and Any Suspension or Termination of IRB Approval [45 CFR 46.103(b)(5)(i) and (ii), 21 CFR 56.108(b)(1)(2) and (3)]

31. Reviewing information about unanticipated problems involving risk to human subjects or others

Section 31.1 describes what constitutes an unanticipated problem involving risk to subjects or others, including adverse events that require reporting to the IRB. Section 31.2 outlines specific documents submitted to the IRB regarding an unanticipated problem. Section 31.3 discusses the process for reviewing unanticipated problems and the range of actions the IRB may take based on the review. Section 31.4 provides an overview of how to determine whether the IRB approved informed consent form requires revision based on the information about the unanticipated problem.

31.1 Unanticipated Problems and Adverse Event

For research regulated by the Common Rule, unanticipated problems include any incident, experience, or outcome that meets all of the following criteria:

  1. The incident is unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related outcomes, such as the IRB approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
  2. The incident is related or possibly related to participation in the research (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 incident suggests that the research places the research subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Examples of unanticipated problems include, but are not limited to:

  1. An actual unforeseen harmful or unfavorable occurrence to subjects or others that relates to the research protocol (injuries, side effects, deaths);
  2. A problem involving data collection, data storage, privacy, or a breach of confidentiality;
  3. A subject complaint about IRB approved research procedures;
  4. New information about a research study (e.g., a publication in the literature, interim findings, safety information released by the sponsor or regulatory agency, or safety monitoring report) that indicates a possible increase in the risks of the research;
  5. Changes in approved research initiated without IRB review and approval to eliminate apparent immediate hazards to the subject;
  6. Incarceration of a subject related to the participation in the research;
  7. A sponsor-imposed suspension of a protocol due to possible increased risk;
  8. A complaint from a subject when the complaint indicates potential increased risk or when the complaint cannot be resolved by the PI;
  9. A protocol deviation that places one or more subjects at increased risk or has the potential to occur again; and
  10. An event that requires prompt reporting to the sponsor.

For FDA-governed research and as a subset of unanticipated problems, adverse events include events that are unexpected, serious and would have implications for the conduct of the study (e.g., requiring a significant and usually safety-related change in the protocol such as revising inclusion/exclusion criteria, including a new monitoring requirement, modifying the informed consent, or altering the PI's brochure). Adverse events involve risks to the research participant or others. They are often unfavorable medically related events, including any abnormal sign, symptom, or disease temporarily associated with the subject’s participation in the research or clinical trial. Examples of adverse events include, but not limited to:

  1. Death,
  2. Congenital anomaly,
  3. Birth defect,
  4. Hospitalization,
  5. The prolongation of a hospitalization, or
  6. A life-threatening event.

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31.2 Documents Submitted

The PI is responsible for submitting to the IRB Chair the following:

  1. A written summary of the unanticipated problem,
  2. The outcome of the unanticipated problem; and
  3. Any steps taken to prevent recurrence of the unanticipated problem.

The PI must report the serious adverse events to the IRB within twenty-four (24) hours. The PI must report all other adverse events and unanticipated problems to the IRB within five (5) working days. The IRB must submit IND safety reports and an attestation—that the PI has reviewed the safety report—to the FDA by the last business day of the month during which the IND safety report was received.

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31.3 Reviewing Anticipated Problems

Upon receipt of the unanticipated problem, the IRB Chair or his/her designee will perform an initial review to determine whether the report likely represents an unanticipated problem that meets the regulatory criteria which requires reporting to federal oversight agencies (e.g. OHRP, FDA). Upon determining the unanticipated problem likely will require reporting to federal oversight agencies, the IRB Chair or his/her designee will convene an IRB meeting. If the reported problem does not meet the regulatory criteria for reporting to federal agencies, the IRB will handle the issue administratively. The IRB will review all reports to determine if there are issues of possible noncompliance.

Prior to the convened meeting, the IRB will distribute copies of relevant documents to the IRB members for review. The convened IRB will consider whether the event meets the following regulatory criteria for an unanticipated problem involving risks to subjects or others:

  1. The event was unforeseen;
  2. The event is related or possibly related to the research; and
  3. The event caused harm to subjects or placed them at increased risk of harm.

Upon discussion, the IRB will determine whether the event represents an unanticipated problem involving risks to subjects or others. It will determine whether the Institutional Official must report the unanticipated problem to the appropriate regulatory agency (OHRP or FDA). If the IRB determines that the event does not require reporting to the regulatory agencies, the IRB will handle the issue administratively. The meeting minutes will document the IRB’s deliberations and determinations.

For any unanticipated problem that increases the risk for research participants and others, the convened IRB may consider substantive changes to the following:

  1. The research protocol to mitigate the unanticipated problem
  2. Modifications in the consent document/process to inform the research participants; or
  3. Other corrective actions to protect the safety, welfare, or rights of subjects or others.

In addition, the IRB and the PI may consider the following corrective actions in response to an unanticipated problem:

  1. Changes to the protocol initiated by the PI prior to obtaining IRB approval to eliminate apparent immediate hazards to subjects may need to be made a permanent part of the protocol;
  2. Modification of inclusion/exclusion criteria to mitigate the newly identified risks;
  3. Implementation of additional procedures for monitoring subjects, the consent process, and/or the research;
  4. Suspension of enrollment of new subjects;
  5. Suspension of research procedures on currently-enrolled subjects;
  6. Modification of the protocol;
  7. Modification of the continuing review schedule;
  8. Modification of informed consent documents to include a description of newly recognized risks or any other information that should be disclosed during the consent process;
  9. Notification of current subjects when such information may relate to subjects’ willingness to continue;
  10. Provision of additional information about newly recognized risks to previously enrolled subjects;
  11. Require the investigator to re-consent current participants;
  12. Termination of the protocol with consideration for health and well-being of currently enrolled subjects; and
  13. Referral to other organizational entities.

Upon the completion of the review, the IRB will notify the PI in writing. If the problem/event does not require the reporting to federal agencies, the letter will acknowledge this determination. If the problem/event requires reporting to the regulatory agencies, the letter will inform the PI of the following:

  1. This determination that the problem/event meet the criteria which requires reporting to the federal agencies;
  2. Accordingly, the problem/event will be reported to the appropriate federal agency; and
  3. A list of required actions and/or changes to the protocol or consent form.

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31.4 Modification of Informed Consent

To the extent that an unanticipated problem or event occurs and it may impact current or future research participants, the IRB will require that the consent form be modified. The modified consent form will communicate in understandable language the unanticipated problem or event to the research participants. It will provide all the information that a reasonable person would want to have in order to make an informed decision about whether to participate (see 45 CFR § 46.116). The research team must use the modified form to re-consent current participants and to consent all future participants.

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32. Reviewing information about serious or continuing noncompliance with the regulations or IRB requirements and determinations

Section 32.1 provides an overview of what constitutes serious or continuing noncompliance that requires reporting to the IRB. Section 32.2 discusses the specific documents submitted to the IRB regarding serious or continuing noncompliance. Section 32.3 describes the process for reviewing reports of serious or continuing noncompliance and the range of actions the IRB may take based on the review. Section 32.4 outlines the process to determine whether the IRB-approved informed consent form requires revision based on the information about the serious or continuing noncompliance.

32.1 Non-Compliance

Non-compliance is the failure to act in accordance with University policies, IRB policies and procedures, and federal, state, or local laws that govern human subject research. Examples of serious non-compliance include, but are not limited to the following:

  1. Actions that increase risk to participants and/or adversely affect their rights and welfare;
  2. Actions or activity that have harmed research participants or that may cause injury (physical, psychological, emotional etc.);
  3. Actions or activity that has compromised privacy and confidentiality of research participants or compromised ethical principles;
  4. Actions or activity that decrease potential benefits or compromise the integrity or validity of the research;
  5. Conducting human subject research without prior IRB review;
  6. Substantive modifications to IRB approved research carried out without IRB approval;
  7. Enrollment of subjects who fail to meet the inclusion criteria of the protocol or who meet exclusion criteria;
  8. Enrollment or continued participation of research subjects while study approval has lapsed;
  9. Enrollment of research subjects without approved informed consent; and/or
  10. Willful or knowing misconduct by the principal investigator or study personnel.

Examples of continuing non-compliance include, but are not be limited to, the following:

  1. Repeated instances of failure to follow federal regulations and/or university and/or IRB policies and procedures particularly after the IRB has informed the principal investigator and his/her personnel of the problem(s) and that corrective action needs to be taken;
  2. The PI has multiple problems with non-compliance over a lengthy period of time or has a problem with multiple existing or previously approved studies;
  3. A pattern of minor non-compliances with multiple studies by the same investigator(s) that reflect a lack of knowledge, apparent unwillingness to comply with IRB requirements, or a lack of commitment by the investigator and/or study team that, if unaddressed, may compromise the integrity of the human research or the human subjects' protection program; and/or
  4. Actions that suggest the likelihood that non-compliance will continue without intervention.

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32.2 Reporting Misconduct

The IRB encourages those who are aware of potential misconduct by researchers to report their concerns to the IRB Chair or the Provost. University employees and students must report their concerns promptly. The IRB will maintain a climate that fairly evaluates reports of potential misconduct and protects the whistleblower from retaliation. Whistleblowers and PIs are encouraged to provide the following types of information:

  1. A written summary of the noncompliance;
  2. The outcome of the noncompliance, and
  3. Any steps taken to prevent the recurrence of the noncompliance.

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32.3 Investigation Process

The IRB will review and investigate all reports of noncompliance. The IRB will report serious and continuing noncompliance issues to appropriate University supervisors, granting agencies, and regulating agencies. The IRB Chair or his/her designee will review information relating to noncompliance. The IRB Chair or his/her designee will determine if further investigation is necessary. The IRB Chair or his/her designee may obtain information from sources other than the PI.

The IRB Chair or his/her designee will initiate the investigation within seventy-two (72) hours of receiving a report of potential non-compliance. The IRB Chair may request assistance from the IRB members, staff, or University administration. The IRB Chair will create a file of the noncompliance investigation. This file will contain the name of the PI, the project title, IRB protocol number (if assigned), and pertinent information associated with the noncompliance investigation. In addition, the IRB Chair may create a separate file for all documents, which may be included in a report. In the instance of multiple reports associated with the same study, the IRB Chair may store the non-compliance records in one file.

If the IRB Chair or his/her designee determines that there are noncompliance practices or other circumstances that may immediately jeopardize the safety and welfare of human subjects, the IRB Chair or his/her designee will convene a subcommittee of the IRB. Members of this subcommittee may meet either in-person or by teleconference. Based on a majority vote of the present members, the subcommittee may suspend the research until the full IRB can review the noncompliance practice. The IRB Chair or his/her designee will only vote in cases of tied results.

If the IRB Chair or his/her designee determines the noncompliance is not serious and continuing, the IRB Chair or his/her designee may determine and require the PI to implement corrective measures. The IRB will maintain any resulting records for a minimum of three (3) years. If the PI is not in agreement with the findings and corrective action, the PI may appeal the matter in accordance with PPM 4-34b.

If the IRB Chair or his/her designee determines the report of noncompliance is likely serious and/or continuing, the IRB Chair or his/her designee may convene an emergency IRB meeting. During this emergency meeting, the IRB will review and discuss the potential noncompliance. The majority vote of the convened IRB will determine the corrective action required. The IRB may suspend or terminate research using the policies and procedures outlined in these Written Procedures. The meeting minutes will document the IRB decision.

The PI may appeal the board's decision in keeping with PPM 4-34b. The IRB Chair or his/her designee will communicate the information to the Institutional Official (currently the Provost). The IRB will retain records of the IRB's determination and documentation associated with the noncompliance for at least three (3) years following the last date of correspondence associated with the noncompliance. Within seventy-two (72) hours of the convened meeting, the IRB Chair or designee will report the board's decision in writing to following parties

  1. The PI,
  2. The PI's immediate supervisor,
  3. The Institutional Official (currently the Provost), and
  4. The Office of Sponsored Projects (in the case of funded research).

The IRB may send written notification electronically, via postal mail, or by other means.

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32.4 Modification of Informed Consent

To the extent that the noncompliance may impact current or future research participants, the IRB will require that the consent form be modified. This modified consent form will communicate in understandable language the noncompliance to the research participants. It will also provide all the information that a reasonable person would want to have in order to make an informed decision about whether to participate (see 45 CFR § 46.116). The research team will then use the modified form to re-consent current participants and to consent all future participants.

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33. Identifying who is responsible for promptly reporting to the IRB, appropriate institutional officials, any department or agency head, OHRP and/or FDA

The PI and university employees are responsible for promptly reporting IRB related matters to the IRB. The IRB is responsible for reporting pertinent information to the Institutional Official. The Institutional Official (currently the Provost) will report cases of unanticipated problems, serious and/or continuing noncompliance, suspension or termination of IRB approval to applicable federal agencies. The Institutional Officer will report to the applicable funding agencies within one (1) month after the IRB made a determination, unless the matter is under appeal. The Institutional Officer may delay reporting:

  1. If the PI indicates the intent to appeal the decision, and
  2. If the Institutional Official approves a delay in reporting until the appeal has been adjudicated.

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34. Suspending or terminating approval of research that is not being conducted in accordance with the regulations or IRB requirements

Section 34.1 describes when the IRB will consider suspending or terminating IRB approval. Section 34.2 considers what happens to subjects already enrolled in the study if the study is suspended or terminated. Section 34.3 outlines how subjects are informed of the suspension or termination. Section 34.4 describes the orderly termination of the study, or transfer of the study or study subjects, if applicable.

34.1 Suspension or Termination

Common reasons for suspending or terminating a research protocol or research activities include, but are not limited to, instances when the research:

  1. Has led to or is associated with an unexpected increase in risks of harm to subjects;
  2. Is associated with subject injuries; and
  3. Is not being conducted in accordance with IRB requirements (researcher noncompliance).

The IRB may suspend or terminate any research based on:

  1. Information received during its continuing review;
  2. From the findings of a quality improvement visit; or
  3. From complaints made to the IRB.

A PI should always be aware of subject safety issues. The PI should suspend research activities on a study in order to remove immediate hazards to subjects. If hazards cannot be eliminated by modifying the study (e.g., the study design or inclusion/exclusion criteria), the PI must terminate the study. PIs must notify the IRB in writing immediately after suspending or terminating a study. The IRB will review reports of suspensions or terminations. The IRB will determine the following:

  1. Whether the PI must take further actions to protect the research participants; and
  2. To whom the IRB must report the suspension/termination.

The IRB Chair can suspend or terminate IRB approval of a study prior to a convened IRB meeting. The IRB Chair may suspend or terminate IRB approval in the following instances:

  1. The research presents immediate hazards to the research subjects; or
  2. The research team is likely noncompliant and this noncompliance results in an increased risk for the research subjects.

The IRB Chair must consider the protection of the rights and welfare of currently enrolled subjects (e.g., making arrangements for medical or other care of subjects). The IRB Chair will promptly notify the PI of his/her decision immediately. The PI will promptly submit a response to the IRB Chair’s concerns. At a convened meeting of the IRB, the IRB Chair will do the following:

  1. Provide an overview of the suspension/termination;
  2. Discuss the reasons for the decision;
  3. Review the PI’s response to the suspension/termination; and
  4. Lead an IRB discussion of the action, response, and possible further required actions.

The IRB will report the suspension/termination to the Institutional Official and others as deemed necessary.

At a convened meeting, the IRB may suspend research activities or terminate research involved in the following circumstances:

  1. Reports of unanticipated problems involving risks to subjects and others (including adverse events);
  2. Other reports that relate to subject safety in a particular protocol; and
  3. Reports of serious or ongoing noncompliance by the PI and/or research team.

The IRB will notify the PI of the decision promptly. Then the PI will submit promptly a response to the IRB’s concerns. At a subsequent convened meeting of the IRB, the IRB will do the following:

  1. Review the PI’s response to the suspension/termination;
  2. Discuss the response; and
  3. Consider possible further actions required to lift the suspension or rescind the decision to terminate the research.

The IRB will report the suspension/termination to the Institutional Official.

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34.2 Current Enrolled Participants

Upon the suspension or termination of research, the IRB will require the PI to develop and implement a plan for notifying and safely withdrawing current subjects. This plan will take the subjects’ rights and welfare into account and outline the mechanisms to notify former subjects of the suspension/termination. This plan will include any follow-up that may be required to assure the subjects’ ongoing safety. This plan will include reporting mechanisms to notify promptly the IRB of any adverse events or outcomes resulting from the suspended/terminated research.

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34.3 Notification of the Enrolled Participants

As indicated in Section 34.2, the PI will be responsible for developing a plan to notify the enrolled participants. The PI should develop a plan that is likely to notify the enrolled participants in a timely manner and provide the participants with information that a reasonable person would like to know about the suspension or termination. This notification should include information on how to contact the PI if the participants have questions or have experienced unanticipated events. To the extent practicable to provide prompt notice, this initial notification should be in writing in a language that is understandable to the subject or their legally authorized representative. However, the research team may communicate orally in the initial notification, but must subsequently provide written notification as described in the aforementioned sentence.

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34.4 Orderly Wind Up

To ensure the orderly termination of the study, or transfer of the study or study subjects, as applicable, the PI will develop a plan as described in Section 34.2. This plan will place special considerations on the welfare of the enrolled participants.

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35. The timelines required for reporting each type of reportable event to the IRB, to the appropriate institutional officials, any department or agency head, OHRP and/or FDA

In accordance with 45 CFR § 46.108(4), the PI must promptly notify the IRB according to the following timelines:

  1. Study-related death or Serious Adverse Event: twenty-four (24) hours;
  2. Other Unanticipated Problems or Adverse Events: five (5) business days from the date of discovery;
  3. Protocol Deviations/Violations: five (5) business days from the date of discovery;
  4. Anticipated Problems:
    1. a) Expedited: include with next continuing review;
    2. b) Exempt Studies: contact the IRB for additional guidance; and
  5. IND safety reports must be submitted, along with the attestation (IND Safety Report form) that the principal investigator has reviewed the safety report, to the IRB by the last business day of the month in which the IND safety report was received.

The IRB must promptly communicate all reportable events to the Institutional Official as proscribed by these Written Procedures. The Institutional Official will report any reportable events of serious and/or continuing noncompliance to applicable agencies. This Institutional Official will report to the applicable agencies within one (1) month after the IRB determination. The Institutional Official may delay reporting:

  1. If the PI indicates intent to appeal the decision; and
  2. If the Institutional Official (currently the Provost) approves a delay in reporting until the appeal has been fully adjudicated.

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Section V: Additional Considerations and Suggestions for Policies/Procedures

A. Scope and Authority

36. The scope of the IRB written procedures

The University charges the IRB with monitoring these Written Procedures and PPM 4-34b, and related PPMs as assigned by the Institutional Official. The IRB will ensure that these Written Procedures, PPM 4-34b, and related PPMs are consistent with federal regulations governing research involving human subjects.

The IRB may materially revise the Written Procedures only after each IRB members have opportunities to review and comment on the revisions. After such a review and comment period, the IRB Chair may put into effect the material revisions to these Written Procedures. The IRB will provide the University notice of the revisions to the Written Procedures. The IRB may provide this notice by posting the Written Procedures online on the University IRB webpage.

Any IRB member may propose new PPMs or revisions to existing PPMs. If there is a significant revision, the IRB must review and vote on the revisions to the PPM at a convened meeting. The IRB Chair may make minor revisions to PPMs with the authorization of the Institutional Official. Once a majority vote of IRB members in a convened meeting approve the PPM, the IRB forwards the modifications to the Institutional Official (the Provost) for review and approval. Should the Institutional Official reject the PPM, the Intuitional Official will return the PPM to the IRB for additional review along with any comments/suggestions. The IRB may repeat this process after there is a majority vote for the revised or new PPM. Once the Institutional Official has approved the PPM, it must follow the customary University PPM approval process. After the University finalizes the PPM, the University records and distributes the PPM in accordance with its procedures.

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37. The institutional authority under which the IRB is established and empowered, and the independence afforded the IRB to carry out its duties

In accordance with the University PPM 4-34b, the IRB is established and empowered:

[A]s the leader of the institution’s human subjects’ protection program and as having full jurisdiction over all research conducted with human subjects by WSU faculty, staff, or students, whether funded or unfunded. The IRB has full authority to disapprove, modify, or approve studies in keeping with ethical and sound research design and in adherence to the guiding principles of the IRB. The IRB can implement or modify policies and procedures only by a vote of the Board at a convened meeting. New policies and policy modifications adopted by the IRB also must be approved by the Provost. The IRB must disseminate modified policies and procedures to the university community.

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38. The ethical principles which govern the IRB in assuring that the rights and welfare of subjects are protected

The Belmont Report undergirds the ethical principles, which govern the IRB to protect the rights and welfare of research subjects. In 1974, Congress enacted the National Research Act (P.L. 93-348) establishing a National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. In 1979, the National Commission published the now well-known Belmont Report that identified three basic ethical principles for human research, which are:

  1. Respect for Persons,
  2. Beneficence, and
  3. Justice.

The Belmont Report identifies two components of the principle respect for persons:

  1. “[F]irst, that individuals should be treated as autonomous agents,” and
  2. “[S]econd, that persons with diminished autonomy are entitled to protection.”

The report describes beneficence in the following manner:

  1. Ensuring “persons are treated in an ethical manner,”
  2. “[R]especting their decisions,”
  3. “[P]rotecting them from harm,” and
  4. “[M]aking efforts to secure their well-being.”

The general rules of beneficence are:

  1. “[D]o no harm” and
  2. “[M]aximize possible benefits” and
  3. “[M]inimize possible harms.”

The Belmont Report formulates the last principle justice in the following manner:

  1. “[T]o each person an equal share,”
  2. “[T]o each person according to individual need,”
  3. “[T]o each person according to individual effort,”
  4. “[T]o each person according to societal contribution,” and
  5. “[T]o each person according to merit.”

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39. Important regulatory definitions that guide the IRB’s review processes and procedures

For procedures controlled by the Common Rule, these Written Procedures incorporate by reference the definitions found in 45 CFR § 46.102 including:

  1. Certification means the official notification by the institution to the supporting Federal department or agency component, in accordance with the requirements of this policy, that a research project or activity involving human subjects has been reviewed and approved by an IRB in accordance with an approved assurance.
  2. Clinical trial means a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health related outcomes.
  3. Department or agency head means the head of any Federal department or agency, for example, the Secretary of HHS, and any other officer or employee of any Federal department or agency to whom the authority provided by these regulations to the department or agency head has been delegated.
  4. Federal department or agency refers to a federal department or agency (the department or agency itself rather than its bureaus, offices or divisions) that takes appropriate administrative action to make this policy applicable to the research involving human subjects it conducts, supports, or otherwise regulates (e.g., the U.S. Department of Health and Human Services, the U.S. Department of Defense, or the Central Intelligence Agency).
  5. Human subject means a living individual about whom an investigator (whether professional or student) conducting research: (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens. (2) Intervention includes both physical procedures by which information or biospecimens are gathered (e.g., venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes. (3) Interaction includes communication or interpersonal contact between investigator and subject. (4) Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public (e.g., a medical record). (5) Identifiable private information is private information for which the identity of the subject is or may readily be ascertained by the investigator or associated with the information. (6) An identifiable biospecimen is a biospecimen for which the identity of the subject is or may readily be ascertained by the investigator or associated with the biospecimen.
  6. Institution means any public or private entity, or department or agency (including federal, state, and other agencies).
  7. IRB means an institutional review board established in accord with and for the purposes expressed in this policy.
  8. IRB approval means the determination of the IRB that the research has been reviewed and may be conducted at an institution within the constraints set forth by the IRB and by other institutional and federal requirements.
  9. Legally authorized representative means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research. If there is no applicable law addressing this issue, legally authorized representative means an individual recognized by institutional policy as acceptable for providing consent in the non-research context on behalf of the prospective subject to the subject’s participation in the procedure(s) involved in the research.
  10. Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
  11. Public health authority means an agency or authority of the United States, a state, a territory, a political subdivision of a state or territory, an Indian tribe, or a foreign government, or a person or entity acting under a grant of authority from or contract with such public agency, including the employees or agents of such public agency or its contractors or persons or entities to whom it has granted authority, that is responsible for public health matters as part of its official mandate.
  12. Research means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program that is considered research for other purposes. For example, some demonstration and service programs may include research activities. For purposes of this part, the following activities are deemed not to be research: (1) Scholarly and journalistic activities (e.g., oral history, journalism, biography, literary criticism, legal research, and historical scholarship), including the collection and use of information, that focus directly on the specific individuals about whom the information is collected. (2) Public health surveillance activities, including the collection and testing of information or biospecimens, conducted, supported, requested, ordered, required, or authorized by a public health authority. Such activities are limited to those necessary to allow a public health authority to identify, monitor, assess, or investigate potential public health signals, onsets of disease outbreaks, or conditions of public health importance (including trends, signals, risk factors, patterns in diseases, or increases in injuries from using consumer products). Such activities include those associated with providing timely situational awareness and priority setting during the course of an event or crisis that threatens public health (including natural or man-made disasters). (3) Collection and analysis of information, biospecimens, or records by or for a criminal justice agency for activities authorized by law or court order solely for criminal justice or criminal investigative purposes. (4) Authorized operational activities (as determined by each agency) in support of intelligence, homeland security, defense, or other national security missions.
  13. Written or in writing, for purposes of this part, refers to writing on a tangible medium (e.g., paper) or in an electronic format.

For purposes of procedures subject to the FDA, the Written Procedures incorporates by reference the definitions found in 21 CFR § 50.103 including:

  1. Clinical investigation means any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or is not subject to requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that are subject to the provisions of part 58 of this chapter, regarding nonclinical laboratory studies.
  2. Investigator means an individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.
  3. Sponsor means a person who initiates a clinical investigation, but who does not actually conduct the investigation, i.e., the test article is administered or dispensed to or used involving, a subject under the immediate direction of another individual. A person other than an individual (e.g., corporation or agency) that uses one or more of its own employees to conduct a clinical investigation it has initiated is considered to be a sponsor (not a sponsor-investigator), and the employees are considered to be investigators.
  4. Sponsor-investigator means an individual who both initiates and actually conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject. The term does not include any person other than an individual, e.g., corporation or agency.
  5. Human subject means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient.
  6. Institution means any public or private entity or agency (including Federal, State, and other agencies). The word facility as used in section 520(g) of the act is deemed to be synonymous with the term institution for purposes of this part.
  7. Institutional review board (IRB) means any board, committee, or other group formally designated by an institution to review biomedical research involving humans as subjects, to approve the initiation of and conduct periodic review of such research. The term has the same meaning as the phrase institutional review committee as used in section 520(g) of the act.
  8. Test article means any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 and 354-360F of the Public Health Service Act (42 U.S.C. 262 and 263b-263n).
  9. Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
  10. Legally authorized representative means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research.
  11. Family member means any one of the following legally competent persons: Spouse; parents; children (including adopted children); brothers, sisters, and spouses of brothers and sisters; and any individual related by blood or affinity whose close association with the subject is the equivalent of a family relationship.
  12. Assent means a child's affirmative agreement to participate in a clinical investigation. Mere failure to object should not, absent affirmative agreement, be construed as assent.
  13. Children means persons who have not attained the legal age for consent to treatments or procedures involved in clinical investigations, under the applicable law of the jurisdiction in which the clinical investigation will be conducted.
  14. Parent means a child's biological or adoptive parent.
  15. Ward means a child who is placed in the legal custody of the State or other agency, institution, or entity, consistent with applicable Federal, State, or local law.
  16. Permission means the agreement of parent(s) or guardian to the participation of their child or ward in a clinical investigation.
  17. Guardian means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care.

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40. Other relevant federal regulations that may apply to human subject research

To the extent research is subject to other related federal laws, the PI and IRB committee members should consult with University General Counsel to ensure compliance with these laws. Such related laws may include but not limited to the following:

  1. Health Insurance Portability and Accountability Act (HIPPA);
  2. Family Educational Rights and Privacy Act (FERPA);
  3. Gramm–Leach–Bliley Act (GLBA); and
  4. Title 17 of the United States Code (Copyright Law).

PIs conducting research in other countries ought to be familiar with and seek guidance from University General Counsel on laws related to their research inquiries (e.g. General Data Protection Regulation (GDPR)).

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41. Which institutional office(s) or official(s) is responsible for further review and approval, or disapproval of research that is approved by the IRB

No university official or committee may set aside or overrule a determination by the IRB. This includes the disapproval research or the requirement to make modifications in order for the researcher to secure approval for proposed research. Subject to generally applicable principles of academic freedom, the University may determine not to conduct research that the IRB has approved for various reasons including but not limited to the following reasons:

  1. A satisfactory contractual agreement could not be reached with a sponsor;
  2. The research would require resources that the University could not provide;
  3. The research would not be consistent with the University's mission or values; or
  4. The research could expose the University to unacceptable liability.

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42. The IRB’s relationship to the administration of the institution, the other committees and department chairpersons within the institution, the research investigators, other institutions, and the regulatory agencies

The IRB operates in partnership with the Office of Sponsored Projects and reports to the Institutional Official, who is currently the Provost. The University has one IRB member who is not otherwise affiliated with the institution and not part of the immediate family of a person who is affiliated with the University. Otherwise, the IRB members are comprised by faculty and staff members of the University who have research experience with human subjects either as scientists or nonscientists. The IRB members may collaborate on research with researchers from other universities and industry partners. Due to the University’s geographic remoteness to the Washington, DC Metropolitan Area, the IRB members generally do not have many ties with the regulatory agencies who are located in DC.

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B. IRB Membership

43. The number of IRB members required to serve on the IRB

In accordance with 45 CFR § 46.107, IRB will have at least five members with varying backgrounds. At least one member will be nonscientist. The IRB will have a least a scientist. It will also have a member who is not otherwise affiliated with the institution and not part of the immediate family of a person who is affiliated with the University.

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44. Ensuring a diversity in the IRB membership

The University will consider diversity as criteria when making appointments for IRB. The University will recruit researchers with varied expertise as IRB members to ensure that these members can adequately review most research on campus. When appointing nonscientists, the University will consider the professional backgrounds of these nonscientists and will prefer individuals with legal and compliance backgrounds. The University will not only seek IRB members with a diversity in professional experiences, but will consider additional factors such as gender, ethnicity, sexual orientation, age, and sensitivity to community values.

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45. Selecting and appointing the IRB chairperson, the members, and alternate members, if any

Section 45.1 discusses the following: the length of term or service, description of duties, attendance requirements, and performance evaluation for IRB members. Section 45.2 describes the qualifications of the IRB chairperson, members and any alternates, including which alternates can substitute for which IRB members. Section 45.3 outlines the process to determine which members of the IRB, and alternates, are categorized as scientist, nonscientist, and nonaffiliated members.

45.1 Scope and Terms of Service

The Institutional Official will appoint all IRB members including alternates, with recommendations from the IRB Chair, the potential appointees’ supervisors, and the IRB Compliance Officer. These appointments will last one (1) year and will automatically renew upon the anniversary of the appointment date for subsequent terms. These appointments will end when one of the following occurs:

  1. The IRB member decides to step down by providing sufficient notice for the IRB to find a replacement;
  2. The IRB Chair requests that an IRB member steps down; or
  3. The IRB Chair or the IRB member provide at least ten (10) day notice to the other party of the intention to end the appointment prior to the anniversary of the appointment date.

While attendance is not mandatory at every IRB meeting, an IRB member’s regular lack of attendance may motivate the IRB Chair to not renew the appointment of the member or request the IRB member to step down.

There are no systemized performance evaluations for IRB members. However, the IRB may review its members’ determinations during audits of research protocols. Where there are concerns about IRB members’ performances, the IRB Chair may do the following:

  1. Consult with the respective IRB members in question;
  2. Investigate the concerns about the IRB members;
  3. If necessary require additional training, so that the IRB members can more effectively perform their roles; or
  4. Request that the IRB members step down from their role or not renew their appointment.
45.2 Qualifications

The IRB Chair, IRB members, and alternates should have sufficient background to review human subject research. IRB members must be knowledgeable about institutional commitments, regulations, applicable laws, standards of professional conduct, and practice. Members will represent a diversity of race, gender, and cultural backgrounds and will be sensitive to community attitudes. Members will possess the professional competence necessary to review specific research activities. The community representatives will not otherwise be affiliated with the university. All members who represent academic units are university employees who are either full-time faculty members or full-time professional staff and who have experience in higher education. The Institutional Official may select full time administrators to serve. At least one member of the IRB will be a non-scientist, and one will be a member of the community.

45.3 Scientist and Nonscientist

At the University, there is not a systemized approach to make determinations of whether an IRB member is a scientist or nonscientist. The University will make these determinations on a case-by-case basis using the following criteria:

  1. the IRB member’s scope of employment;
  2. His/her education; and
  3. His/her previous experiences.

For an example, the University will generally consider IRB members, who in the scope of their work conduct human research, to be scientists unless other factors make them more likely to be a nonscientist. Scientists may include:

  1. Faculty with human research backgrounds;
  2. Staff involved in institutional research; and
  3. Other personnel with backgrounds in human research.

Nonscientists include individuals whose scope of employment are not associated with human research such as lawyers, accountants, and other professionals. While nonscientists need not have experience performing human research, some background in human research is preferable for all IRB members.

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46. Defining what constitutes conflict of interest for the IRB chairperson, members, alternates, and how the IRB manages any such conflict of interest

No member of the IRB may participate in the review and approval process for any project in which he or she has an actual or potential conflict of interest. The IRB members must disclose any conflict of interest. The IRB will excuse any IRB member or alternate whose name appears anywhere in the application or who has any reason to believe that he or she will have a role in the research. Any IRB member or alternate who feels he or she might not be completely objective in doing the review for any reason may excuse himself or herself. IRB members are encouraged to abstain from votes on protocols where their relationship with the researcher(s) may appear to compromise their objectivity.

Prior to the discussion of protocols at a convened meeting, the IRB Chair may ask if any member has a conflict of interest with any protocol to be reviewed at that meeting. Should an IRB member declare involvement in any way in a research protocol under review by the IRB or state a conflict of interest with the research protocol the following is required:

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

The IRB minutes will document that these requirements have been met.

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47. Training and education of the IRB chairperson, IRB members, alternates, administrative support staff, and investigators (including any orientation, continuing education, and a list of any reference materials provided as a resource)

All IRB members must complete the required human subjects training upon their appointment to the IRB and every three (3) years for the duration of their membership. Initial training consists of the completion of the CITI Program modules required for IRB members. The IRB Chair may remind members in need of completing their triennial training of this requirement. Failure to complete the training may result in removal from the IRB. The IRB may distribute continuing educational materials at each IRB meeting such as periodicals or articles. The IRB may make available webinars and local conferences to the IRB members to attend.

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48. Determining which member(s) may be designated by the IRB chairperson to perform expedited review on behalf of the IRB, and the criteria used to select such designee(s)

The designated initial reviewers of expedited review are:

  1. The IRB Chair,
  2. The Subcommittee Chairs over each college,
  3. The IRB Compliance Officer; and
  4. Other IRB members so designated by the IRB Chair.

The University may select these designated reviewers in consultation with the dean over the respective college based on the individuals’ experience conducting human research. The designated initial reviewers may request any IRB committee member to be the second reviewer. In general, the University selects IRB members based on their familiarity with conducting human research and/or their understanding of the research regulations.

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C. IRB Functions and Operations

49. Administrative support staff duties

Currently, there is only one staff member responsible for the operational functions of IRB, which is the IRB Compliance Officer. The IRB Compliance Officer is primarily responsible for:

  1. Updating the FWA,
  2. Otherwise communicating with the OHRP and the FDA, and
  3. Ensuring general compliance with human research.

To the extent the University hires or appoints other staff to perform IRB duties, the roles and duties of the IRB administrative staff may change based on the scope of their work assignments.

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50. Any additional IRB considerations or requirements when reviewing sponsor-investigator research

Prior to approving a protocol that involves a sponsor-investigator, the IRB must be satisfied that the sponsor-investigator is knowledgeable about his/her responsibilities and has adequate policies and procedures in place to comply with the FDA regulatory requirements. As proscribed by Title 21 Code of Federal Regulations Part 812, these FDA requirements include:

  1. The selection of research staff qualified by training and experience;
  2. The commitment to personally conduct or supervise the investigation according to the research plan;
  3. The selection of study monitor(s) qualified to monitor the progress of the project;
  4. The maintenance of accurate, complete and current records;
  5. The completion of regulatory filings, including amendments (supplemental applications);
  6. Timely submission of the following reports:
    1. i. Unanticipated adverse device effects (10 working days of learning of event),
    2. ii. Progress (regular intervals, but no less than annually),
    3. iii. Current investigator list (6-month intervals),
    4. iv. Recall and device disposition (30 working days after request is made), and
    5. v. Final Report (within 30 days of completion or termination of investigation).

The IRB may also contact or site visit the sponsor-investigator as deemed necessary. At least on an annual basis as part of the continuing review, the IRB will conduct a review designed to evaluate the instigator-sponsor’s compliance with the FDA regulatory requirements.

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51. Keeping the IRB informed of study completion and close out

The PI must submit the closing report in writing to the IRB Chair either by hardcopy or electronically. The closing report should briefly do the following:

  1. Describe the research that occurred,
  2. Report the findings of the study, and
  3. Provide pertinent information related to subject participation.

The IRB requests that the PI transmit the report within thirty (30) days of the conclusion of the research. In instances where the report has not been received by the time of continuing review (for expedited or full review approved studies), the IRB Chair may remind the PI of his/her obligation to provide this report.

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52. The use of consultants by the IRB

When necessary, the IRB may invite individuals with competence in special areas to assist in the review of issues. Any IRB committee member may suggest the need for a consultant. The IRB Chair will review the request for a consultant. If the IRB Chair deems the consultant necessary, the IRB Chair will request authorization from the Institutional Official. The Institutional Official may then grant or deny this request. The IRB will secure the consultant consistent with Utah procurement law and the University procurement policies. The consultants may attend convened IRB meetings or provide written memoranda with regards to research protocols. However, these individuals may not count towards a quorum or vote with the IRB.

Unless the University has a member of the IRB who is a prisoner or a prisoner representative with an appropriate background and experience to serve in that capacity, the University will need to secure a consultant to satisfy the requirement of Subpart C of Title 45, Part 46. In the absence of choosing a consultant who is a prisoner or has been a prisoner, the IRB will choose a prisoner representative who has a close working knowledge, understanding, and appreciation of prison conditions from the perspective of the prisoner.

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53. Registering the IRB and maintaining IRB registration through the HHS Internet-based registration system

The IRB Compliance Officer is responsible for ensuring that the IRB maintains its registration and FWA through the HHS registration system.

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54. Informing investigators of the IRB requirements and procedures

The IRB will distribute the requirements and procedures to potential PIs and will communicate with them directly on an individualized basis as necessary. The IRB may distribute the requirements and procedures through a webpage. This webpage may include these Written Procedures.

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55. Contingency plans for transferring oversight of one or more studies to another institution or IRB in the event that the IRB is unable to continue oversight of the study

When transferring IRB review and oversight of a research protocol from one IRB to another IRB, the IRB will use the FDA’s “Guidance for IRBs, Clinical Investigators, and Sponsors: Considerations When Transferring Clinical Investigation Oversight to Another IRB FDA” as a persuasive guide to determine the reasonable actions to implement this transfer (see Guidance Transferring IRB Oversight). In accordance with this guidance document, the IRB will enter into a written agreement with the other IRB unless the other IRB is a division of the University. As applicable, the agreement will specify how the IRBs will handle and document the following steps:

  1. Identify those studies for which IRB oversight is being transferred;
  2. Ensure the availability and retention of pertinent records;
  3. Establish an effective date for transfer of oversight, including records, for the clinical investigation(s);
  4. Conduct a review of the study(ies) by the receiving IRB, where appropriate, before it accepts responsibility for the study(ies);
  5. Confirm or establish the date for the next continuing review;
  6. Determine whether the consent form needs to be revised;
  7. Notify the key parties;
  8. Update IRB registration information; and
  9. Outline any other relevant or necessary step to effectuate the transfer

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D. IRB Records

56. A list of the records maintained by the IRB

In order to allow a reconstruction of a complete history of IRB actions related to the review and approval of protocols, the IRB records will include the following:

  1. Protocol applications, research protocols, consent documents and all other documents submitted for review of proposed human subject research;
  2. Scientific evaluations, when provided by an entity other than the IRB;
  3. Progress reports submitted by researchers;
  4. Reports of injuries to participants;
  5. Data and safety monitoring reports, if any;
  6. Modifications to previously approved research;
  7. Unanticipated problems involving risks to subjects or others;
  8. Documentation of noncompliance;
  9. Significant new findings;
  10. Meeting Minutes;
  11. Continuing Review Activities;
  12. the IRB membership rosters; and
  13. IRB written procedure

The IRB will retain records related to IRB operations (as well as research related records) for at least three (3) years and as proscribed by the data retention schedules maintained at the Utah State Archives.

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57. A description of where records are stored and how records are stored

The IRB will store records in either paper or electronic format in a centralized data repository so long as the data storage is consistent with University PPM 10-1.

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58. Preparing and maintaining minutes of IRB meetings

Minutes of IRB meetings will document the following:

  1. Documents reviewed by the IRB;
  2. The attendance at the meetings;
  3. Actions taken by the IRB;
  4. The vote on these actions, including the number of members voting for, against, and abstaining;
  5. The basis for requiring changes in or disapproving research;
  6. A written summary of issues of dispute and their resolution; and
  7. Any adverse events reviewed.

The minutes will also document any discussion with respect to adverse events/unanticipated problems/IND safety reports. The minutes will also include a list of all protocols reviewed and approved for initial, continuing review, or amendment. The minutes may also include the IRB votes on changes to policies and procedures. The IRB Compliance Officer will keep the minutes.

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59. Ensuring that records are retained for at least 3 years after completion of the research and that they are organized and accessible for inspection

The IRB will retain all research related records for a period of at least three (3) years from the date a study concludes and consistent with the data retention schedules maintained in the Utah State Archives. The IRB will store the records in a centralized repository.

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