WSU Guidelines Manual: Human Subjects in Research

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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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 ipso facto to not be research. This is not within the plain reading of the regulation. OHRP interpretations of the definition do not justify this interpretation. 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.

Based on the cannon of construction for statutes “expressio unius est exclusio alterius,” it is unlikely that classroom activities are categorically excluded from the definition of research. When participating federal agencies revised the definition of research for the Revised Common Rule, these agencies did not explicitly exclude classroom activities from its definition as it did with the four categories outlined above.

The Supreme Court has recognized the doctrine “expressio unius est exclusio alterius,” which translated from Latin into English means "the express mention of one thing excludes all others.” In Barnhart v. Peabody Coal Co., the Supreme Court held this doctrine “has force only when the items expressed are members of an "associated group or series," justifying the inference that items not mentioned were excluded by deliberate choice, not inadvertence” (see Barnhart v. Peabody Coal). In this instance, the courts would likely hold that the excluded categories of research are an “associated group or series.” According to legal precedent, the inference is then justified that classroom activities were “excluded by deliberate choice”; and consequently, classroom activities are not ipso facto excluded from research.

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.

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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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