RCATT at NDSU

The IRB at NDSU is administered through the Office of Sponsored Programs Administration, within the Office of the Vice President for Research, Creative Activities and Technology Transfer. The IRB Office is located in the Research and Technology Park, at 1735 NDSU Research Park Drive, phone number 701-231-8908. The IRB Office includes an Executive Director and support staff.

The Vice President for Research, Creative Activities, and Technology Transfer appoints the Executive Director, who is a member of the staff in the Office of Sponsored Programs Administration. Responsibilities of the Executive Director include the initial review of all research projects, assignment of projects into appropriate review categories (Exempt Certification, Expedited Review, or Full Board Review), and follow-up to ensure IRB project approval. Other duties include certification that qualified projects are eligible for exemption, organization of IRB meetings, development and distribution of meeting minutes, coordination of all IRB record keeping activities, maintaining federal assurances, and development and presentation of investigator training sessions.

The Executive Director is a permanent member of the IRB, and serves as the Human Protections Administrator named in the Federal-Wide Assurance on file with OHRP.

The Vice President for Research, Creative Activities and Technology Transfer serves as the Institutional Official legally authorized to represent the institution on all assurance documents.

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2. Composition of the IRB

Composition of the NDSU IRB follows the minimum guidelines set forth in the Code of Federal Regulations, 45 CFR 46, as follows:

45 CFR 46.107, IRB Membership.
(a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.

(b) Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the institution's consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist entirely of members of one profession.

(c) Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas.

(d) Each IRB shall include at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution.

(e) No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.

(f) An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of issues which require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB.

Food and Drug Administration (FDA) regulations at 21 CFR 56.107 contain the same IRB membership requirements for reviewing research involving products regulated by the FDA

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3. Selection, Appointment of Members

Selection
Institutional Members: Each college, using whatever administrative and electoral procedures are appropriate to that unit, nominates and recommends to the Vice President for Research, Creative Activities, and Technology Transfer a candidate to serve as that college's representative to the IRB.

Non-affiliated Members: Are recommended for appointment by the Vice President for Research, Creative Activities, and Technology Transfer, with the advice and consent of a simple majority of IRB members present and voting at the meeting during which such candidates are considered. The names and credentials of nominees for non-affiliated members shall be presented to the IRB not less than 14 days prior to their formal consideration and election.

Additional Members: may be added to the IRB at the recommendation of the IRB Chair and the Vice President for Research, Creative Activities and Technology Transfer. The addition of new members will follow the appropriate selection procedures described above.

Appointment
Faculty appointments to the IRB are not automatic or routine. The Vice President for Research, Creative Activities, and Technology Transfer must approve a nominee and officially appoint said person to serve as college representative to the IRB. Conversely, the Vice President for Research, Creative Activities and Technology Transfer can disapprove the college's recommendation of a nominee and request another nominee of that college's choosing.

Since non-affiliated members are nominated by the Vice President for Research, Creative Activities, and Technology Transfer, their appointment to the IRB is automatic upon acceptance by the IRB as detailed above.

The Chair of the IRB is a direct appointment of the Vice President for Research, Creative Activities, and Technology Transfer and serves at the request of that office. The Chair must be at least an academic-year appointment member of the NDSU faculty with a degree at the doctoral level. Appointment of Chair is renewable in September of each academic year.

The Vice-Chair is elected by a majority of those IRB members present and voting at the regular September meeting of the IRB. At least one faculty member of the IRB shall be nominated by any member of the IRB (self-nomination appropriate), followed by a period of time sufficient to allow for consideration and evaluation of candidates. The Vice-Chair shall serve in that capacity for a period of one year, at which time re-election occurs or a new Vice-Chair is elected.

The Vice-Chair shall preside at meetings on those occasions when the Chair is unable to attend an IRB meeting or is an investigator on a research project being reviewed or considered by the IRB. The Vice-Chair has all associated responsibilities an obligations of the Chair whenever the Chair is incapable of serving in that capacity. Except when serving as acting Chair, the Vice-Chair shall have the same duties and responsibilities as any IRB member.

In the event that both the Chair and the Vice-Chair are unavailable to chair a meeting of the IRB, a regular board member previously designated as "substitute Vice-Chair" by the Chair and the Vice President for Research, Creative Activities and Technology Transfer, shall act as Chair for the meeting, and has all responsibilities and duties associated with the office of Chair for that meeting. Such temporary status as substitute Vice Chair continues until either the Chair or Vice Chair become available to handle IRB matters.

Terms of Office (Tenure)
Each appointed member of the IRB shall serve a regular term of office of three years. At the expiration of an institutional member's term-of-office, the member's college Dean shall either re-nominate him/her or offer another candidate. The re-nomination or selection process of an NDSU representative shall occur according to his/her unit's appropriate administrative procedures. As with "new" members, a re-nomination is subject to the approval of the Vice President for Research, Creative Activities and Technology Transfer.

At the expiration of a non-affiliated member's term of office, the member may be asked by the Vice President for Research, Creative Activities, and Technology Transfer to serve another term, or another off-campus representative may be appointed.

Members of the IRB always have the option of not serving their full term (i.e., resigning). Such vacancies shall be filled according to procedures outlined above for new and re-nominated members.

Representatives of colleges are appointed on a "staggered" basis so that there are always experienced members serving on the board.. Positions will be filled as vacated, each with a three-year term of office, beginning in September of the year appointed.

Alternate Members
Each IRB member will have a designated alternate, with similar background and experience, available to vote at meetings or perform reviews in their absence. The selection, appointment and term conditions for alternates are the same as for regular members. Alternate members are welcome to attend any meeting of the IRB, and will vote in the absence or recusal of their regular, designated member.

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4. Original Schedule of Appointments

(October 13, 1986)
In order to have membership renewal or replacement of board members on a "staggered" basis, the following appointment scheme will be employed. Year indicated is the year in which that position is first up for renewal, unless the position becomes vacant (through resignation or departure from university service) beforehand:

Agricultural Experiment Station	1988
College of Agriculture	1988
College of Engineering & Architecture	1988
College of Science & Mathematics	1988
College of Humanities & Social Sciences	1987
College of Pharmacy	1987
*College of Home Economics	1987
*School of Education	1987
College of Business Administration	1987

**NDSU Extension Service	1989
Physician member	1989
Non-NDSU member	1989

Attorney member permanent non-voting
IRB Executive Director permanent non-voting

Vice President for Research, Creative
Activities and Technology Transfer ex-officio (non-voting)

* College of Home Economics, School of Education, and Department of Health, Physical Education and Recreation were combined in 1992 to form the College of Human Development and Education (HDE).

** Representation from the NDSU Extension Service has been discontinued. Their primary mission is education and service and they do very little research in the sense of scholarly activity.

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5. Removal of Members

It is unlikely that a member of the IRB shall ever conduct him/herself in a manner that will invite a consideration for a request for removal from the IRB. However, a member of the IRB can be removed from the Board by the following procedures.

Institutional members can be removed prior to the expiration of their three-year term with a written request for removal submitted to the Vice President for Research, Creative Activities, and Technology Transfer, stating reasons why such person should no longer serve the university community as an IRB member. Approval of this request by the Vice President for Research, Creative Activities, and Technology Transfer and the Chair of the IRB is required.

Non-affiliated members of the IRB can be removed with the direct approval of the Vice President for Research, Creative Activities, and Technology Transfer, the Chair of the IRB, and no fewer than three additional members of the IRB.

The Chair of the IRB serves at the request of the Vice President for Research, Creative Activities and Technology Transfer, who may present a request for removal to the IRB. The Chair can only be removed from that office by a majority vote of the full IRB. A recommendation for removal cannot be issued directly from anyone other than the Vice President for Research, Creative Activities, and Technology Transfer. If removed as Chair, that faculty member retains regular IRB membership as a college representative for the duration of his/her term.

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6. IRB Meeting Procedures

A regular meeting of the IRB shall occur once a month in those months in which protocol(s) requiring Full Board review have been submitted. Additional special meetings may be called at the discretion of the Chair. Members shall be informed of regular meetings with a yearly schedule provided by the IRB Executive Director. Special meetings may be called with short notice, but such meetings must have the majority of the members of the IRB present, including at least one member whose primary concerns are in non-scientific areas. In order for the research to be approved, it shall receive the approval of a majority of those members present at the meeting.

Research projects which require review by the full board must be reviewed at a convened meeting in which a quorum (simple majority) of IRB members is present, including at least one member whose primary concerns are in nonscientific areas.

The IRB Chair shall prepare the agenda and direct the meeting accordingly. The following meeting format shall be followed:

1. Call to order
2. Announcements
3. Approval of minutes of previous meeting
4. Old business
5. New business
6. Adjournment

Review and Consideration of Protocols
Whenever possible and desirable, the principal investigator (P.I.) or his/her designee shall be present at that portion of the meeting in which his/her proposal is under consideration, in order to clarify relevant portions of the protocol and project.

Members of the IRB are authorized to ask any questions pertaining to the study in order to reach a conclusion regarding risks, benefits, safety, and protection of human participants, in accordance with applicable federal regulations and institutional policies.

If a member has a conflict of interest (investigator or co-investigator, financial, department level, or personal relationship) that would affect their ability to consider the rights and welfare of participants in the protocol being reviewed, they may provide information regarding the project, but may not serve as a primary reviewer. The conflicted member must leave the room during voting, and voice the nature of their conflict.

The review of protocols involving a vulnerable population with which members of the board may have little experience, may require the opinion of an outside consultant. The consultant would review the research project for acceptability with this subject group, but would not vote with the IRB.

Voting Procedures and Options
After an adequate period of discussion of the research protocol, the Chair may call for a "motion to consider," at which point any IRB member may move for one of the following:

APPROVAL:	protocol and consent form(s) are satisfactory as presented, and investigator may begin research immediately.
APPROVAL, contingent on minor modifications:	project is not satisfactory as submitted; specific,minor modifications and/or alterations to protocol and/or consent form(s) are required, as specified by the IRB. These modifications would involve specific changes requiring only simple concurrence by the investigator. Revisions and modifications to the satisfaction of the IRB Chair (acting on behalf of the IRB) may then result in APPROVAL.
DEFERRAL:	insufficient information to reach any definitive conclusion regarding the protocol, or the IRB requires more than minor modifications for approval.. Investigator will be asked to revise the protocol and resubmit for full IRB review at a later meeting.
DISAPPROVED:	protocol places subjects at unacceptable risk relative to benefits; research project as designed and described is not suitable for involvement of human participants.

Once the "motion to consider" has been seconded, there will be opportunity for further discussion and clarification. The motion can then be voted upon.

In order for the reviewed research to be approved, it must receive the approval of a majority of those members present. Tied votes are considered not approved, and protocols are returned to the investigator for alterations and modifications necessary to obtain approval. In any case, the motion at hand must pass by a simple majority of those present.

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7. Minutes of IRB Meetings

The Code of Federal Regulations requires the following minimum information to be included in IRB meeting minutes:

45 CFR 46.115 (2), IRB Records. Minutes of IRB meetings shall be in sufficient detail to show attendance at the meetings; actions taken by the IRB; the vote on these actions, including the number of members voting for, against, and abstaining; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution.

FDA regulations at 21 CFR 56.115(2) have the same requirements for research involving FDA-regulated products.

These minutes shall serve as IRB records of full board review proceedings. All remarks, commentaries, opinions, and votes of board members are eligible to become part of the official record of the meeting. Minutes will reflect the presence/absence of IRB members and recusal in the case of a conflict of interest. For each protocol reviewed, the minutes must also state the risk level, risk/benefit ratio, approval category (for research involving children), and the basis for determining the continuing review period.

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8. IRB Review of Research

The Code of Federal Regulations requires the following minimum criteria for IRB review of research. NDSU IRB review and approval procedures are covered in more detail in Part B: Project Submission, Review, and Approval.

45 CFR 46.109 IRB Review of Research.
(a) An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities covered by this policy.

(b) An IRB shall require that information given to subjects as part of informed consent is in accordance with Sec. 46.116. The IRB may require that information, in addition to that specifically mentioned in Sec. 46.116, be given to the subjects when in the IRB's judgment the information would meaningfully add to the protection of the rights and welfare of subjects.

(c) An IRB shall require documentation of informed consent or may waive documentation in accordance with Sec. 46.117.

(d) An IRB shall notify investigators and the institution in writing of its decision to approve or disapprove the proposed research activity, or of modifications required to secure IRB approval of the research activity. If the IRB decides to disapprove a research activity, it shall include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing.

(e) An IRB shall conduct continuing review of research covered by this policy at intervals appropriate to the degree of risk, but not less than once per year, and shall have authority to observe or have a third party observe the consent process and the research.

FDA regulations at 21 CFR 56.109 have similar requirements, with the exception of Sec. 56.109(c):

An IRB shall require documentation of informed consent in accordance with Sec. 50.27 of this chapter, except as follows: (1) The IRB may, for some or all subjects, waive the requirements that the subject, or the subject's legally authorized representative, sign a written consent form if it finds 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 the research context; or (2) The IRB may, for some or all subjects, find that the requirements in Sec. 50.24 of this chapter for an exception from informed consent for emergency research are met.

In order to determine that all substantive and relevant changes in protocol and/or consent documents are being reported, and in order to verify compliance with IRB regulations, the IRB shall have the authority to physically inspect any research premises or review all research documents relating to the protocol and procedures being used in human participant experimentation. Generally, the investigator will be asked to provide copies of relevant and necessary documents for IRB review. Such document requests are in addition to that generated in a project progress report. In most cases, this will only occur when there is an indication that a substantive change is in effect which has not been reported. Failure to comply with such a request for information from the IRB may result in suspension or termination of IRB approval of research.

45 CFR 46.113, Suspension or termination of IRB approval of research. An IRB shall have authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall include a statement of the reasons for the IRB's action and shall be reported promptly to the investigator, appropriate institutional officials, and the (appropriate federal) department or agency head.

45 CFR 46.112, Review by institution. Research covered by this policy that has been approved by an IRB may be subject to further appropriate review and approval or disapproval by officials of the institution. However, those officials may not approve the research if it has not been approved by an IRB.

FDA regulations at 21 CFR 56.113 are similar, but require reporting of suspensions or terminations to the Food and Drug Administration. FDA regulations at 21 CFR 56.112 are the same as those of HHS.

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9. REGULATORY REPORTING REQUIREMENTS

As outlined in the terms of the Federal-Wide Assurance with OHRP (Written Procedures):

The Institution should establish, and should provide a copy to OHRP upon request, written procedures for:
1) ensuring prompt reporting to the IRB, appropriate institutional officials, the relevant Department or Agency Head, any regulatory body, and OHRP of any: (i) unanticipated problems involving risks to subjects or others, (ii) serious or continuing noncompliance with the Federal Regulations or IRB requirements, and (iii) suspension or termination of IRB approval. (45 CFR 46.103(b)(5) and 21 CFR 56.108(b).)

The IRB will file a report to the Department of Health & Human Services Office of Human Research Protections (OHRP) (and the Food and Drug Administration, if applicable to the research study), in the event of injury and/or other unanticipated risks to subjects or others that occur with any activities related to human subjects research, regardless of funding source, covered under our Federal-Wide Assurance. The report, on IRB letterhead, and signed by the Chair of the IRB and the Vice President for Research, Creative Activities and Technology Transfer will be filed as soon as possible after the date of occurrence.

The university is required to report to OHRP, and any granting agency, the termination of a project due to non-compliance with IRB regulations and directives. OHRP, however, does not require a report in the event of simple failure to submit a continuing review report for a completed project.

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Part B: Project Submission, Review and Approval Process

1. Project Submission

What Activities Require NDSU IRB Review?
In accordance with the terms of the Federal-Wide Assurance from OHRP, NDSU IRB review is required whenever the institution becomes engaged in research involving human subjects/participants. This occurs whenever any NDSU employee (faculty, staff, student, or other individual associated with NDSU) or agent intervenes or interacts with human subjects, or obtains information about human subjects for research purposes. This would include all such investigations conducted at NDSU facilities, as well as those conducted elsewhere by, or under the direction of, any representative of NDSU. Also, IRB review is required whenever NDSU receives a direct award to conduct human subject research, even when the activities are carried out by a subcontractor or a collaborator. (Refer to the OHRP document, 'Engagement of Institutions in Research' , for more information, and specific examples.)

The Code of Federal Regulations, 45 CFR 46, define "research" :
45 CFR 46.102 (d) Definitions. Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

The determination of research involvement should be made conservatively, and the IRB has final authority regarding classification of a particular project as research. In general, any investigation designed to generate results that are intended to be disseminated by publication (e.g. in a journal, book, or disquisition,) or presentation at a professional conference is typically considered research, although this is not the sole factor in making this determination. Research conducted with human participants for masters or doctoral theses must receive IRB approval prior to initiation.

The question of what constitutes research may be especially relevant in relation to activities designed to gather data to evaluate a specific program. Contribution to "generalizable knowledge" may be determined by whether or not the data will be disseminated by means of publication or presentation, although there are other considerations as well. In general, OHRP gives guidance that if the activity will be used to draw conclusions related to a larger entity then the activity is considered 'research'. Therefore, the following considerations should be made.

A program evaluation activity would be 'research' if:

there is an intent to use to data to contribute to generalizable knowledge

results will be used to apply knowledge to other programs.

QA/QI, program evaluation, surveillance, etc. activities would be 'research' if:

they will involve experimental or non-standard interventions;

intent is to use the data to contribute to generalizable knowledge;

are not normally done as part of standard operating procedures;

are subject to peer review (designed to be used outside of the institution).

Typically, classroom exercises do not meet the IRB's definition of research, since they do not contribute to generalizable knowledge. Such classroom research exercises do not require IRB review. However, in teaching research methods, instructors should be cognizant of relevant issues such as voluntary participation and confidentiality of information when designing activities involving human subjects. Please note: If an instructor or student anticipates possibly publishing or presenting results from classroom research exercises (thus, "research" as defined above) he/she must file for IRB review prior to initiating the project, and provide individuals an opportunity to consent to research use of their information. There is no provision for obtaining a retroactive IRB approval.

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The Code of Federal Regulations, 45 CFR 46, define "human subject":
45 CFR 46.102 (f) Definitions. Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information. Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and subject. Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator associated with the information) in order for obtaining the information to constitute research involving human subjects.

NDSU policy goes beyond the federal definition concerning research involving 'identifiable private information'. The NDSU IRB does require a protocol be submitted for the research use of existing data, documents, records, or specimens, whether or not they can be identified. NDSU IRB review is not required, however, if these materials are publicly available (via the library, internet or other public source).

Any study involving a human subject and a product regulated by the FDA must also meet applicable requirements at 21 CFR 50:
21 CFR 50.1 Scope. (a) This part applies to all clinical investigations regulated by the FDA under sections 505(i) and 520(g) of the Federal Food, Drug and Cosmetic Act, as well as clinical investigations that support applications for research or marketing permits for products regulated by the FDA, included foods, including dietary supplements, that bear a nutrient content claim or a health claim, infant formulas, food and color additives, drugs for human use, biological products for human use, and electronic products.

Who Must Submit Projects for NDSU IRB Review?
Any investigator affiliated with NDSU who plans to conduct research involving human participants must file a request for review with the NDSU IRB in time to obtain IRB approval before the research begins, and before any contact is made with prospective participants. IRB approval cannot be granted retroactively.

It is the responsibility of the NDSU investigator to seek and obtain any off-campus IRB approvals required. The NDSU IRB will not act on behalf of any investigator to obtain approval from another institution's IRB.

Approval from another IRB does not substitute for NDSU IRB review and approval. However, to avoid duplication of effort, documentation of review and approval by another institution's qualified IRB may be accepted by NDSU, with a written agreement for the reviewing IRB to abide by the terms of our Federal-Wide Assurance. In addition, the FWA would also require an update to reflect the responsible IRB for the particular project. The NDSU IRB Office requires a complete copy of the protocol, consent form(s), and documentation of the originating IRB approval. If, however, it is determined that some aspect of the protocol or consent form(s) does not meet NDSU IRB requirements, the IRB will notify the investigator of the concern and the action needed to resolve the situation.

Some NDSU personnel serve as professional consultants (as defined in Section 152:1.3 of the NDSU Policy Manual) to off-campus agencies or organizations. Occasionally, such participation involves assisting with design, collection, or analysis of data derived from human participants, or the direct involvement with human participants for the purpose of evaluating a program or service. A faculty or staff member serving as a consultant is responsible for his/her own professional and ethical conduct, and the institution would not be considered to be 'engaged in research'. As stated in Section 152:1.3 of the NDSU Policy Manual, "The University does not assume any responsibility for the professional services rendered during an external professional activity." NDSU IRB review is not required as long as the results of the research activity are for the benefit of off-campus agencies or organization only and not to be used for any NDSU purposes.

However, if the NDSU investigator expects authorship or similar credit, listing an NDSU affiliation, as a result of collaborative research activity, such research arrangements do require NDSU IRB review since the institution would be considered to be 'engaged in research'. In general, any involvement as an NDSU employee or student in project design, subject recruitment, data collection from human participants, or the analysis of identifiable human data requires NDSU IRB review.

NDSU faculty on leave who conduct research involving human participants at another institution must obtain review and approval from a legally constituted IRB, usually at the host or research-site institution, with a copy of the documentation forwarded to the NDSU IRB Office.

NDSU faculty who wish to continue recruiting human participants and/or collecting data from human participants for a research project begun while at their former institution must notify the NDSU IRB Office of their active status on the project and provide IRB documentation. If all subject recruitment and data collection from humans for the ongoing research project is completed by the time the faculty member joins NDSU, NDSU IRB review is not necessary; however, use of existing data for a different research project requires NDSU IRB review.

Researchers from other institutions or organizations, not affiliated with NDSU in any way, who plan to recruit human research participants from certain segments of the NDSU student, staff, or faculty populations, are not required to obtain formal NDSU IRB approval. However, an NDSU employee or student who is asked by an outside researcher to assist in a project by intervening or interacting with individuals, or by providing or obtaining individually identifiable private information must submit a protocol to the NDSU IRB for approval. This level of involvement would typically be considered equivalent to that of a co-investigator or key personnel. Specific examples would include, but are not limited to: agreeing to be a contact person for the study, releasing names of potential participants utilizing private, non-public information, manipulating the environment for research purposes, collecting consent forms or research data, conducting research interviews.

Examples of assistance that would not engage NDSU in research and would not require NDSU IRB approval would include, but are not limited to: performing commercial, non-collaborative services that would not result in publication privileges, informing potential subjects about research, or providing information about a study (without obtaining consent, or acting as a representative of the investigator), permitting use of facilities for investigators to interact with participants, Consult the IRB for any questions regarding specific projects.

Visiting faculty from another institution who conduct research involving human participants while at NDSU must obtain NDSU IRB approval.

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Protocol Submission Procedures
Investigators should file a request for IRB review well before the planned research is to begin. The Principal Investigator may make an initial determination of the type of form to use ('Request for Exempt Certification' or 'Request for Expedited/FullBoard Review'). Protocol submissions lacking information, or not in the required format, will be returned to the investigator prior to IRB review. For exempt projects, allow at least a week for IRB exempt certification. Expedited review takes at least two weeks. If many changes are required to consent forms or protocols, expect three to four weeks to obtain approval from expedited review. Projects to be reviewed by the full board must be submitted to the IRB at least two weeks prior to the next scheduled IRB meeting, which is normally held during the second week of each month. Full Board review of a project could take up to a month from the time the project is initially submitted to the IRB Office until final approval is given. Any changes required to be made the protocol and/or consent form(s) as a result of IRB review will take additional time on the part of the investigator and the IRB. Investigators are strongly encouraged to submit requests for IRB review well in advance of the proposed project start date. For example, if you want to begin recruiting subjects in May, submit your request for IRB review in time for the April IRB meeting, which is normally the second week in April. That will give you at least two to three weeks following IRB review to make revisions and obtain final IRB approval before the project begins in May.

Requests for IRB review of research projects should be submitted to the IRB Office, 1735 NDSU Research Park Drive, Research and Technology Park. The mailing address for requests originating off-campus is: IRB, Office of Sponsored Programs Administration, North Dakota State University, P.O. Box 5756, Fargo, ND 58105-5756.

2. IRB Review Catagories

Research projects submitted to the IRB for approval are screened by staff in the IRB Office and placed in one of three review categories: exempt, expedited review, or full board review. This section describes procedures for submission, review, and approval within each category, including an explanation of the review and approval processes.

Exempt Certification
Research activities involving human participants in which there is minimal or no risk and in which the only involvement of human participants would be in one of the criteria described below may be considered by the IRB Office to be exempt from further IRB review. Projects that qualify for exempt status must, however, receive formal written certification of such exempt status. This certification, which is obtained from the IRB Office, serves as an assurance that the project 1) qualifies for exempt status in accordance with federal regulations, and 2) is designed to ensure that the rights and welfare of human participants are protected. Investigators wishing to obtain exempt certification of a project should complete and submit to the IRB Office, along with appropriate attachments, a Request for Exempt Certification Form. Instructions for required attachments are included on the form. Investigators may initiate the study only after receipt of written notification of exempt certification from the IRB Office; exempt certifications will expire 3 years after this date.

Exempt project design requirements. In order to meet criteria for exempt certification, projects must be designed to include certain minimum standards set forth in federal regulations covering human participant research. Of primary importance among these standards is informed consent. The basic elements of informed consent (45 CFR 46.116(a)) must be communicated to each prospective subject, unless adequate justification has been provided for a waiver of this requirement. Informing participants may be accomplished by means of a consent form or by a cover letter or information sheet attached to the questionnaires to be distributed. For telephone surveys or face-to-face interviews, the elements of informed consent may be communicated orally. When the elements of informed consent are to be given orally, the investigator must develop a written script of the oral presentation. The script should be submitted to the IRB Office along with the completed Request for Exempt Certification Form.

Obtaining the signed consent of subjects participating in exempt research projects is generally not required, although the NDSU IRB reserves the right to require signed consent of participants for certain exempt projects. Nevertheless, it may be desirable to obtain signed consent for two reasons: 1) having the documented consent (a signature) of participants in the investigator's possession is good insurance if a problem or question should arise about a participant's involvement; and 2) students who will be involved in human research in their professional careers will undoubtedly be required to obtain signed consent of subjects. Learning the process with university research projects will assist them in becoming familiar with the federal regulations that they will be required to follow later in their careers. When signed consent will be obtained from participants, the required format for consent forms must be followed, omitting those elements of informed consent that do not apply to the project. The format is described in Section II, 'Requirements for Informed Consent'.

Criteria for exempt status certification. As stated in the Code of Federal Regulations (45 CFR 46.101(b)), research activities in which the only involvement of human participants will be in one or more of the following categories may be certified by the IRB Office as exempt:
1. Research conducted in established or commonly accepted educational settings, involving normal education practices, such as (i) research on regular and special education instructional strategies; or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.*1,2

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

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

5. Research and demonstration projects which are conducted by or subject to the approval of Department or Agency heads, and which are designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs.

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

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In determining whether a research project qualifies for exempt status, the following requirements should also be considered:
1. If an adult participant's only involvement in a research project is the completion of survey instruments or interview procedures in which the participant is asked to give his/her "natural" responses to questions, free of any prompting or other interventions, the project will normally be considered exempt.

2. If the investigator attempts to influence or change participants' behavior, perception, or cognition, the project cannot qualify for exempt status.

3. Research projects involving prisoners are not eligible for exemption.

4. Research projects involving FDA regulated products are not eligible for exemption.

Expedited Review
Research activities involving no more than minimal risk and in which the only involvement of human participants will be in one or more of the categories described in this section may be reviewed by the expedited review procedure. 'Minimal risk' is defined in the Code of Federal Regulations at 45 CFR 46.102(i) and 21 CFR 50.3(k):

Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

Federal regulations give the following requirements for the expedited review procedure:

45CFR 46.110(b) (and 21 CFR 56.110(b)): An IRB may use the expedited review procedure to review either or both of the following:

(1) some or all of the research appearing on the list (of research categories published in the Federal Register, and re-printed below) and found by the reviewer(s) to involve no more than minimal risk,

(2) minor changes in previously approved research during the period (of one year or less) for which approval is authorized.

Under an expedited review procedure, the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB. In reviewing the research, the reviewers may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in accordance with the non-expedited procedure set forth in 46.108(b) (21 CFR 56.108(c)).

The NDSU IRB supplements the federal regulations with the following policy: All protocols within the Expedited REview category will be administratively screened by the Executive Director or IRB staff and reviewed by the chair, or at least one IRB member, as assigned by the IRB chair. If a reviewer has concerns about a project, the Executive Director will attempt to resolve the concerns through communication with the investigator. If a reviewer's concerns cannot be resolved to his or her satisfaction, the protocol must be referred to the Full Board for review at a convened meeting.

Categories of Research that may be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure (Source: Federal Register, Volume 63, No. 216, pg. 60364, November 9, 1998)

Applicability

(A) Research activities that (1) present no more than minimal risk to human subjects, and (2) involve only procedures listed in one or more of the following categories, may be reviewed by the IRB through the expedited review procedure authorized by 45 CFR 46.110 and 21 CFR 56.110. The activities listed should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human subjects.

(B) The categories in this list apply regardless of the age of subjects, except as noted.

(C) The expedited review procedure may not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects= financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.

(D) The expedited review procedure may not be used for classified research involving human subjects.

(E) IRBs are reminded that the standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review--expedited or convened--utilized by the IRB.

(F) Categories one (1) through seven (7) pertain to both initial and continuing IRB review.

Research Categories

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

(a) Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.)

(b) Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

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

(a) from healthy, nonpregnant 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

(b) from other adults and children2, 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: (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) supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization.

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

Examples: (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject=s privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (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 nonresearch purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(4) This listing refers only to research that is not exempt.)

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

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

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

(a) where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or

(b) where no subjects have been enrolled and no additional risks have been identified; or

(c) where the remaining research activities are limited to data analysis.

(9) Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories 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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Reporting expedited reviews. The Code of Federal Regulations has the following requirement for reporting expedited reviews:

45CFR 46.110(c) (and 21CFR56.110(c): Each IRB which uses an expedited review procedure shall adopt a method for keeping all members advised of research proposals which have been approved under the procedure.

The NDSU IRB complies with this requirement by including in the agenda items for each meeting a list of all projects received by the IRB Office since the last meeting, and the manner in which each project was reviewed and approved (i.e., exempt, expedited, or full board review).

Number of copies. Investigators wishing to obtain IRB approval of a non-federally-funded project by the expedited review procedure should submit to the IRB Office, with appropriate attachments, an original and two copies of a completed and signed "Request for Expedited or Full Board Review" protocol form. Appropriate attachments include consent form(s), copies of survey instruments, letters from cooperating entities, advertisements to be sent to the media, or any material to be distributed to subjects. Expedited review and approval normally takes about two weeks. Investigators will be notified in writing of IRB project approval or of any changes that may be required for project approval.

Informed Consent. The signed consent of participants is required for all projects that are subject to expedited review, unless the IRB has approved a waiver of this requirement. See the following excerpt from the Code of Federal Regulations:

45 CFR 46.116, General requirements for informed consent. Except as provided elsewhere in this policy, no investigator may involve a human being as a subject in research covered by this policy unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An investigator shall 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 shall 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.

Research projects under the jurisdiction of FDA have similar requirements (21 CFR 50.20), however, informed consent may be waived in emergency situations, as described in Sec. 56.23 and Sec. 56.24.

Consent forms must include the elements of informed consent described in Section II of this manual, written in the required format with subheadings as described. When projects are submitted to the IRB Office for expedited review, the consent form(s) will be reviewed for content and format, along with the project description. Consent form(s) and protocols that do not conform to the required format, or containing insufficient information, will be returned to the investigator for revision before being distributed to the IRB reviewers.

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Full Board Review
Research projects that do not qualify for exempt certification or expedited review must be reviewed by the full board at a convened meeting of the IRB. IRB meetings are typically scheduled for the second week of each month; schedules are posted on the IRB webpage. Projects to be reviewed by the full board must be submitted to the IRB Office no later than two weeks prior to the next scheduled IRB meeting to allow adequate time for review of the protocol.

Number of copies. Investigators wishing to obtain IRB approval of a project by the full board review procedure are to submit a signed original, and 13 copies of the "Request for Expedited or Full Board Review" protocol form and appropriate attachments. Appropriate attachments include consent forms, copies of survey instruments, letters from cooperating entities, advertisements to be sent to the media, and any material to be distributed to participants. The IRB is also required to review any related grant application(s) submitted to an external agency.

Protocol description. The protocol should describe the interactions, interventions, or other involvement of human subjects, and be written in lay language, avoiding technical terms and jargon, so that it is understandable to a non-scientific member of the IRB, and anyone unfamiliar with the particular field of study.

Informed Consent. The signed consent of participants is required for all projects that are subject to full board review, unless the IRB approves a waiver of this requirement. See the following excerpt from the Code of Federal Regulations:

45 CFR 46.116, General requirements for informed consent. Except as provided elsewhere in this policy, no investigator may involve a human being as a subject in research covered by this policy unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An investigator shall 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 shall 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 waiver 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.

Research projects under the jurisdiction of FDA have similar requirements (21 CFR 50.20), however, informed consent may be waived in emergency situations, as described in Sec. 56.23 and Sec. 56.24.

Consent forms must include the elements of informed consent described in Section II of this manual, written in the required format, with subheadings as described. When projects are submitted to the IRB Office for full board review, the consent form(s) will be reviewed for content and format, along with the protocol. Consent form(s) and protocols that do not conform to the required format, or have insufficient information will be returned to the investigator for revision prior to IRB review.

Full Board review procedures. When the IRB Office determines that a project requires review at a convened meeting, the investigator will be notified in writing of the date, time, and location of the IRB review. The investigator will be requested to be present at the portion of the meeting in which his/her protocol will be reviewed. The protocol will be assigned to a technical reviewer and a consent form reviewer, who may contact the investigator prior to the meeting to clarify any issues. At the IRB meeting, the investigator will be asked to give a short verbal description of the project, and may be asked to answer questions regarding the project. The investigator will then be dismissed, and the IRB Chair will call for a "motion to consider" from Board members. Voting procedures and options are described in Section I, Part A, 5. IRB Meeting Procedures.

Investigators will be notified of the Board's decision within ten days from the date of review. Such notification will be in the form of a letter from the Executive Director, with a copy to the Chair. The letter will describe any changes to the protocol or consent form(s) that are required for final IRB approval. Additional information can be found in Section I, Part B, 4. IRB Approval of Research.

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3.THE IRB REVIEW PROCESS (Expedited and Full Board Reviews)

Criteria for IRB Review of Research The Code of Federal Regulations requires the following minimum criteria for IRB approval of research:

45 CFR 46.111 (and 21 CFR 56.111), Criteria for IRB approval of research.

(a) In order to approve research covered by this policy, the IRB shall determine that all of the following requirements are satisfied:

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

(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility. *1

(3) Selection of subjects is equitable. In making this assessment, the IRB should take into account the purposes of the research and the setting in which the research will be conducted, and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

(4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by Section 46.116 (21 CFR Part 50).

(5) Informed consent will be appropriately documented, in accordance with, and to the extent required by Section 46.117 (21 CFR 50.27).

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

(7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

(b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

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Determination of Risk
The IRB will make a decision based on common sense and sound professional judgment as to whether or not the proposed research places the participant "at risk." A participant is considered to be at risk if he/she is exposed to the possibility of harm, whether physical, psychological, sociological, economic, or other, as a consequence of any activity that goes beyond the application of those established methods necessary to meet his/her needs. The Code of Federal Regulations defines minimal risk:

45 CFR 46.102 (i) (and 21 CFR 56.102(i)): Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

Risk as applicable to federal policy is most obvious in medical or behavioral science research projects involving procedures that may induce a potentially harmful altered physical state or psychological condition. The most obvious examples include invasive procedures, the administration of drugs or radiation, the requirement of strenuous physical exertion, and an intervention that precipitates an emotional disturbance. There are social and behavioral research projects in which, although there may be no immediate risk, procedures may be introduced which constitute a threat to the subject's dignity, right to privacy, or economic welfare. There are also medical and biomedical projects concerned solely with organs, tissues, body fluids, and other materials obtained in the routine performance of medical services, which obviously involve no element of physical risk to the subject, but their use for certain research, training, and service purposes may present psychological, sociological, or legal risks to the subject or authorized representatives. The risk element will also be examined for those studies dependent upon existing information or stored data which may have been obtained for non-research purposes but which, when used in a research context, may present risk to the human participant.

If it is determined that a participant will be placed at risk, the IRB will perform a risk/benefit analysis which involves an assessment of the degree of risk, probability of occurrence, reversibility, and relation to anticipated benefits. The IRB will consider the fact that certain subject populations (e.g., children, pregnant women, prisoners, mentally disabled, physically disabled) may be at greater risk than others.

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Risk/Benefit Analysis

1. In research involving a non-therapeutic intervention, the potential of risk to the participant must be outweighed or balanced by the potential benefit to the subject and/or by the knowledge to be gained.

2. In therapeutic research involving more than minimal risk, the potential risk should be outweighed or balanced by the potential benefit to the participant. In addition, the relation of the anticipated benefit to the risk must be at least as favorable to the subject in the non-research context. No participant is allowed to continue in a research protocol if another therapy of proven better quality becomes available to the subject.

3. In research where a standard therapy not a part of the research protocol is employed solely for the benefit of the participant along with additional procedure performed solely for research purposes, the anticipated benefits of the therapy cannot be used to justify exposing participants to the risks associated with the research procedures. Such risks can only be justified in light of the potential benefits of the research procedures. Conversely, only the risks associated with the research procedures should be used in determining the risk/benefit ratio.

4. In research involving a therapy employed for the potential benefit of a participant suffering from a life-threatening illness, the risk of serious adverse effects may be acceptable providing there are no other therapeutic alternatives available to the subject that offer a more favorable risk/benefit ratio.

5. In research where no direct benefits to the participant are anticipated, the IRB will evaluate whether the risks and/or discomfort presented by procedures performed solely to obtain generalizable knowledge are ethically acceptable.

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Review of Prospective Participant Population
The IRB will review the prospective participant population and must be assured that: (a) the participant population and number of participants is appropriate with respect to the nature and goals of the research, and (b) the selection of participants is equitable with regard to the potential risks and benefits. Some groups are considered to be vulnerable (children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons) and will require extra protections.

Research projects involving children (45CFR46, Subpart D). The Code of Federal Regulations defines children:

45 CFR 46.402 (a): Children are 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.

For research conducted in North Dakota, participants under the age of 18 are considered children. The IRB must find that adequate provisions are made for soliciting the assent of the child and the permission of their parent(s)/guardian(s). The Code of Federal Regulations specifies 3 categories of research involving children that are approvable by the IRB:

45 CFR 46.404: Research not involving greater than minimal risk. DHHS will conduct or fund research in which the IRB finds that no greater than minimal risk to children is presented, only if the IRB finds that adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in 46.408.

45 CFR 46.405: Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects. DHHS will conduct or fund research in which the IRB finds that more than minimal risk to children is presented by an intervention or procedure that 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, only if the IRB finds that:
(a) the risk is justified by the anticipated benefit to the subjects;
(b) the relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches; and
(c) adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians, as set forth in 46.408.

45 CFR 46.406: Research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition. DHHS will conduct or fund research in which 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:
(a) the risk represents a minor increase over minimal risk;
(b) the intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations;
(c) the intervention or procedure is likely to yield generalizable knowledge about the subjects' disorder or condition which is of vital importance for the understanding or amelioration of the subjects' disorder or condition; and
(d) adequate provisions are made for soliciting assent of the children and permission of their parents or guardians, as set forth in 46.408.

Research projects not approvable under the categories listed above, but presenting an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children must be submitted to OHRP for public comment and review by a panel of experts.

Children who are wards of the state require additional protections in order to participate in research, as specified in The Code of Federal Regulations:

45 CFR 46.409 Wards.
(a) Children who are wards of the State or any other agency, institution, or entity can be included in research approved under 46.406 or 46.407 only if such research is: (1) related to their status as wards; or (2) conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards.

(b) If the research is approved under paragraph (a) of this section, the IRB shall require 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 advocate for more than one child. The advocate shall be an individual who has the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child's participation in the research and who is not associated in any way (except in the role as advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.

An advocate would be selected by consultation with the facility where the research is taking place or where subjects will be recruited, to determine who could best serve this role for one or more children. Similar requirements for clinical investigations involving children as subjects are outlined in the FDA regulations at 21 CFR 50, Subpart D.

Research projects involving pregnant women, human fetuses and neonates (45CFR46, Subpart B). The IRB may approve research involving pregnant women or fetuses only if the findings as specified in 45CFR46.204 can be made. Additionally, the IRB may approve research involving neonates only by making the findings specified in 45CFR46.205.

Research involving prisoners (45CFR46, Subpart C). In order to review research involving prisoners, the IRB must have one member serving as a prisoner representative, and a majority of members with no association to the prison(s) involved. These requirements also apply if a participant becomes a prisoner while participating in a research study. 'Prisoner' is defined in the Code of Federal Regulations:

45CFR46.303(c): "Prisoner" means any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.

The definition of 'minimal risk' is slightly different for this subject population:

45CFR46.303(d): Minimal risk is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons.

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The IRB may approve only certain categories of research involving prisoners, as specified in the Code of Federal Regulations:

45CFR46.306: Permitted research involving prisoners.
(a) Biomedical or behavioral research conducted or supported by DHHS may involve prisoners as subjects only if:
(1) the institution responsible for the conduct of the research has certified to the Secretary that the Institutional Review Board has approved the research under 46.305 of this subpart; and

(2) in the judgment of the Secretary the proposed research involves solely the following:

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;

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;

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

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.

(b) Except as provided in paragraph (a) of this section, biomedical or behavioral research conducted or supported by DHHS shall not involve prisoners as subjects.

The IRB has additional duties when reviewing research involving prisoners, as outlined in the Code of Federal Regulations:

§46.305 Additional duties of the Institutional Review Boards where prisoners are involved.

(a) In addition to all other responsibilities prescribed for Institutional Review Boards under this part, the Board shall review research covered by this subpart and approve such research only if it finds that:

(1) the research under review represents one of the categories of research permissible under 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 nonprisoner 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.

(b) The Board shall carry out such other duties as may be assigned by the Secretary.

(c) The institution shall certify to the Secretary, in such form and manner as the Secretary may require, that the duties of the Board under this section have been fulfilled.

A certification is only required for federally funded research.

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Review of Investigator Qualifications
The IRB will review investigator qualifications and may request a cv or resume to be assured that (a) the investigator has the appropriate qualifications and/or licensure to carry out the procedures involving human participants with an acceptable degree of potential risk, and (b) the investigator has adequate facilities and equipment to conduct the research with an acceptable degree of potential risk.

Review of Experimental Design and Scientific Merit
The IRB will review experimental design in order to be assured that the potential risks to the participants are minimized and the potential benefits maximized by using procedures consistent with sound research design.

Review of Informed Consent
The IRB will review the consent procedure and the informed consent form to determine if it conforms to NDSU IRB standards and contains all the appropriate elements of informed consent as required by federal regulations.

4. IRB APPROVAL OF RESEARCH

Notification of Findings
The Code of Federal Regulations gives the following guidelines for IRB approval of research:

45 CFR 46.109 IRB Review of Research. (d) An IRB shall notify investigators and the institution in writing of its decision to approve or disapprove the proposed research activity, or of modifications required to secure IRB approval of research activity. If the IRB decides to disapprove a research activity, it shall include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing.

Research projects subject to FDA regulation have similar requirements (21 CFR 56.109(e), with the exception of investigations involving a waiver of informed consent under Sec. 50.24.

In compliance with this regulation, investigators will be notified of the Board's decision within ten days from the date of review. Notification will be in the form of a letter from the Executive Director, describing the Board's decision:

If APPROVED, the investigator may begin the proposed research project.

If APPROVED contingent on minor modifications, the investigator will be notified of the specific changes to the protocol and/or consent form necessary to obtain IRB approval of the research protocol. The Executive Director of the IRB will communicate, in writing, the findings of the IRB and the necessary modifications, if any, to the principle investigator. The Chair will review the requested specific, minor revisions or modifications. The research may start only after a final approval letter (signed by the Chair, or Vice Chair) has been sent to the investigator(s).

If the investigator does not respond within a reasonable period of time to the IRB's request for specific minor modifications, the proposed project must be resubmitted for full review again. The letter of notification to the investigator will convey these stipulations and time limit.

If DEFERRED, the investigator will be notified in writing that the project as described provides insufficient information to reach a decision for approval or disapproval, or requires more than minor modifications in order to be approved. The investigator will be asked to resubmit for a later regularly scheduled meeting. In addition, the findings of the IRB that resulted in the decision to defer the project will be conveyed in writing to the investigator.

If DISAPPROVED, the reasons for disapproval will be conveyed in writing to the investigator.

Approval period.
The IRB will determine the approval period, appropriate to the degree of risk involved in the project. A progress report will be required at appropriate intervals, but continuing review must occur at least annually. More details can be found in Section I, Part C: Investigator Reporting Requirements.

Certification for Federal Funding. If an investigator intends to submit an IRB-approved protocol to a federal agency for funding, he/she should inform the IRB Office. The IRB Executive Director will follow that agency's procedures for notifying them of IRB approval of the project.

NDSU holds an approved Federal-Wide Assurance (FWA) with the Office of Human Research Protections, and ensures the terms of this assurance are followed by all investigators at our institution. In addition, federal funding agencies may require an assurance identification/IRB certification form, signed by the authorized institutional official, prior to releasing funds for human subjects research. Contact the Office of Sponsored Programs Administration for the proper procedure for a specific granting agency.

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Part C: Investigator reporting Requirements

NDSU IRB policy, and federal regulations require the following written reports from investigators conducting IRB-approved research: (1) continuing review reports, (2) requests for change in protocol/consent form(s), (3) reports of injury/unanticipated events, and (4) project completion reports.

1.Continuing Review Reports

Following is an excerpt from the U.S. Code of Federal Regulations:

45 CFR 46.109(e) (21 CFR 56.109(f)), IRB Review of Research. An IRB shall conduct continuing review of research covered by this policy at intervals appropriate to the degree of risk, but not less than once per year, and shall have authority to observe or have a third party observe the consent process and the research.

All non-exempt research projects involving human participants are approved for a maximum of one year at a time. Occasionally, selected projects will be reviewed more often than annually. Such projects are:

any research involving fetuses;

any research involving human participants for which there have been reports of injury or unanticipated problems as a consequence of participating in the research;

any research for which the IRB had specifically required "more often than annual" review at the time approval was granted;

any research project the IRB deems appropriate to review on a more-often-than-annual basis, including projects not in any of the above categories.

Any project that will not be completed prior to expiration of the IRB approval period must be reviewed and approved by the IRB prior to the expiration date in order to receive continuing approval.

The investigator(s) will be sent a notice for continuing review at least 30 days prior to the anniversary date of his/her project. When the continuing review report is received in the IRB Office, the review will be scheduled, and research will be allowed to continue during the review period unless information contained in the report indicates possible increased risk to subjects. In this instance, the IRB Office will request that the research be suspended until the project has been reviewed and approved by the Full Board; the appropropriate reports will be filed with OHRP, institutional officials, funding and other applicable agencies. If no continuing review or completion report is received by the due date, the IRB Office will send the investigator a notice of overdue report, notifying them of the impending expiration of approval, with a copy to the department chair. The continuing review or completion report must then be submitted immediately, in order to prevent a lapse in approval. For those projects requiring continuing review by the full board, reports must be submitted at least 2 weeks prior to the meeting.

Projects originally reviewed by the full board usually require continuing review by the full board. All members will receive a copy of the continuing review report. A primary reviewer, as assigned by the chair or director, will also review the complete file and provide a review summary at the convened meeting. The IRB will Ongoing projects would qualify for continuing review by the expedited method if: (1) it was originally reviewed by the expedited method, or (2) no new participants will be recruited, all participants have completed the research activities, and the project is active only for long-term follow-up, OR (3) no subjects have been enrolled and no additional risks have been identified. Two IRB members per month will be scheduled for continuing review of expedited protocols. They will have access to the complete protocol file(s) and document their review and comments.review and approve the project using the same criteria applied at the initial review (45 CFR 46.111, and/or 21 CFR 56.111, as applicable).

Ongoing projects would qualify for continuing review by the expedited method if: (1) it was originally reviewed by the expedited method, or (2) no new participants will be recruited, all participants have completed the research activities, and the project is active only for long-term follow-up, OR (3) no subjects have been enrolled and no additional risks have been identified. Two IRB members per month will be scheduled for continuing review of expedited protocols. They will have access to the complete protocol file(s) and document their review and comments.

IRB approval of a continuing review report is effective for an amount of time, no longer than 12 months, determined by the reviewers. The investigator will be notified, in writing, of continuing approval, or additional information or revisions required to gain continuing review of their project.

Format.
Continuing Review Reports should be submitted to the IRB Office, and should include, at a minimum:
. the number of participants initiated into the research project during the period being reported, including the cumulative number of participants since initial approval;
. a description of the experiences of the participants (benefits, adverse reactions, withdrawals from the research );
. the results of the research thus far;
. a current assessment of the risks and benefits based on study results;
. any new information that has come to light since the IRB's last review;
. a copy of all current informed consent or assent forms

"More-often-than-annual" reviews will follow the same reporting and review procedures, with the appropriate changes in reporting intervals and deadlines.

Failure to file a continuing review/completion report. If a continuing review or completion report is not filed with the IRB Office will send the investigator a notice of overdue report, notifying them of the impending expiration of approval. The continuing review or completion report must then be submitted immediately, in order to prevent a lapse in approval. For those projects requiring continuing review by the full board, reports must be submitted at least 2 weeks prior to the next convened meeting.

If a continuing review report or completion report has not been received, reviewed, and approved prior to the IRB approval expiration date, the investigator will be notified in writing that the approval for the indicated research project has expired. The investigator is prohibited from recruiting additional participants and must terminate the project, unless this would be harmful to already enrolled participants. The determination of potential harm should be made promptly by the IRB chair, in consult with the investigator. This termination notice will be signed by the Chair of the IRB and the Vice President for Research, Creative Activities, and Technology Transfer, with a copy to the investigator's Department Chair, and College Dean. If the project is receiving external funding, the funding agency will also be notified of the expiration of IRB approval. However, OHRP does not require a report when a project has simply expired for failure to file a completion report. In addition, the IRB may terminate approval for all of an investigator's ongoing projects. Also, the IRB will not review and approve any new protocol submissions until the investigator has submitted a Completion Report for the expired project. If the investigator wishes to re-establish the project, a new protocol must be filed, and re-reviewed according to NDSU procedures.

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2. Changes to the Protocol or Consent Form(s)

Any proposed change to the IRB protocol or consent form(s), including a change in investigator(s) or key personnel, must be reviewed and approved by the IRB prior to implementation, except where an immediate change is necessary to eliminate hazard to the participant, in accordance with requirements outlined in the Code of Federal Regulations at 45 CFR 46.103 (b)(4)(iii) and 21 CFR 56.108(a)(4). The request for change should be submitted to the IRB Office, and attached to a completed and signed "Request for Change in Protocol/Consent Form(s)", along with a copy of the revised protocol or consent form. The request for a change in protocol should include:

a description of the proposed changes;

justification for the proposed changes;

any additional comments you wish to make relative to the proposed changes;

revised protocol and consent form(s) when appropriate.

If the changes are significant, a completely revised protocol form may be requested, with proposed changes highlighted. Changes will be reviewed initially by the IRB Office, and the investigator will be notified whether the changes require review by the expedited method or by the convened board at the next scheduled meeting. Minor changes (ie, change in research personnel, research site, correction to contact information or grammatical errors) may be administratively approved by the Executive Director. Appropriate steps will be taken in the IRB Office to ensure a timely review and approval of the changes.

Note: A protocol may be changed without prior IRB approval where necessary to eliminate apparent immediate hazards to the participants or others. However, the data collected during this period could not be used for reserach, and the IRB must be notified IN WRITING within 72 hours of any change. Full IRB review is required by the next convened meeting.

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3. Report of Injury or Unanticipated Events

Any research-related injuries (physical or psychological), adverse reactions, complaints, or unanticipated problems (including a breach of confidentiality of study records or data) involving risks to subjects or others during the course of an IRB-approved project must be reported, in accordance with federal regulations at 45 CFR 46.103(b)(5) and 21 CFR 56.108(b)(1). A report must be submitted, in writing to the IRB Office within 72 hours of the occurrence. The report should be a written description of the injury or other event, attached to a completed and signed "Report of Injury/Unanticipated Events Form". Investigators are also strongly encouraged to share such information with their Department Chair and College Dean.

Investigators are encouraged to use their best judgment regarding the nature and degree of a reportable injury or unanticipated problem. In general, anything serious enough to warrant medical or psychiatric intervention is reportable, as are verbal or written complaints of participants in which they proclaim that participation presents substantial discomfort, risk, and/or endangerment beyond that explained to them, or as otherwise stated in the consent form.

Reports of injury/unanticipated events will be reviewed by the IRB Chair or the full board at a convened meeting. The IRB will review the report to determine if the event is serious or non-serious, and expected or unexpected. This finding may or may not require a change to the existing protocol, notification of currently enrolled participants, suspension/termination of the study, or other measures as appropriate.

The IRB is also required to report any unanticipated problems involving risks to subjects or others to the Office of Human Research Protections, any applicable regulatory body (ie, Food and Drug Administration), and the relevant department or agency head.

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4. Project Completion Reports

The completion or termination of a project is considered a change in protocol, and a report is required. As soon as the research portion of a project is finished (analysis of identifiable data is complete), a completion report must be submitted with the following information:

the number of participants initiated into the research project during the period being reported, including the cumulative number of participants since initial approval

a description of the experiences of the participants (benefits, adverse reactions, withdrawals from the research );

a brief summary of results

a current assessment of the risks and benefits based on study results;

any new information that has come to light since the IRB's last review

The file will be placed in inactive status and retained for at least three years after notification of closure.

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Part D: Guidlines for Special Type of Research

1. FDA-Regulated Products

Clinical investigations involving a test article that is subject to regulation by the Food and Drug Administration must comply with FDA informed consent and IRB review regulations (21 CFR, parts 50, 56). As defined in 21 CFR 56.102:

(c) Clinical investigation means any experiment that involves a test article and one or more human subjects. (l) Test article means any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under section 351 or 354-360F of the Public Health Service Act.

Research involving investigational drugs.
An investigational drug may be defined by one of the following:

a drug in any of the clinical stages of evaluation (Phase I, II, III) which has not been released by the FDA for general use or cleared for sale in interstate commerce;

any commercially available drug proposed for a new use;

any commercially available drug to be used in a new dosage, form, or method of administration;

any commercially available drug which contains a new component such as an excipient, coating, or menstruum;

a new combination of two or more commercially available drugs;

a combination of commercially available drugs in new proportions;

any commercially available drug involved in a post-marketing surveillance.

Good medical practice and patient interests require that physicians be free to use commercially available drugs according to their best knowledge and judgment. If a physician uses a drug for an indication not in the approved labeling, he or she has the responsibility to be well informed about the drug and to base its use on a firm scientific rationale and on sound medical evidence, and to maintain records of the drug's use and effects. Use of a drug in this manner as part of the "practice of medicine" does not require review by the IRB or FDA notification despite the fact that the drug is technically classified as investigational.

The investigational use of an approved, marketed product differs from the situation described above. "Investigational use" suggests the use of an approved product in the context of a clinical research study protocol. When the principal intent of the investigational use of a drug is to develop information about its safety or efficacy, IRB review and approval is required.

When a marketed drug is shipped in interstate commerce for the purpose of conducting a clinical trial on the drug for an unapproved use, at an unapproved dosage, by an unapproved route of administration, or in an altered dosage form, the submission of an Investigational New Drug permit (IND) is required. As described in the FDA regulations at 21 CFR 312.2(b)(1), the clinical investigation of a marketed drug or biologic does not require submission of an IND if ALL six of the following conditions are met:

it is not intended to be reported to FDA in support of a new indication for use or to support any other significant change in the label

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Guidelines :: Section I