Wake Forest University--Reynolda Campus

Institutional Review Board Policies and Procedures

Statement of Ethical Principles of Research

Definitions and Applicability

Institutional Responsibilities

Codes of Conduct
Federalwide Assurance
Establishment of an Institutional Review Board
Administrative Oversight
Authorized Institutional Official
Human Protections Administrator

The Institutional Review Board

The Investigator’s Responsibilities

The Institutional Review Board and the Review Process

The IRB and the Review Process
IRB Responsibilities
Levels of Review
Procedures for IRB Review of Research

Informed Consent Process
Amendments
Adverse Events and Unanticipated Problems
Continuing Review
Closure of Approved Research
Noncompliance
Suspension or Termination of IRB Approval
Appealing an IRB Decision

Special Categories of Research and Sensitive Issues

Children in Research Involving Human Subjects
Cooperative and Cross-Campus Research
Internet Research
Cross-Cultural Research
Incomplete Disclosure and Deception in Research
Privacy Protection
Research Involving Sensitive Issues

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Wake Forest University – Reynolda Campus
Institutional Review Board Policies and Procedures

Statement of Ethical Principles of Research

1. The three basic ethical principles for the conduct of human subjects research, as set forth in The Belmont Report (Ethical Principles and Guidelines for the Protection of Human Subjects of Research) of the National Commission for the Protection of Human subjects of Biomedical and Behavioral Research, shall guide all research involving human subjects on the Reynolda Campus of Wake Forest University (WFU).
   

   Respect for Persons. Individuals participating in research shall be treated as autonomous human beings. Extra protection shall be provided to those with limited autonomy. Beneficence: Research shall be designed in a manner that maximizes benefits and minimizes harms. Justice: Research shall be designed so that its burden and benefits are distributed equitably. Individuals shall be treated fairly.

2. Promulgated by the Department of Health and Human Services, these ethical principles, codified as Title 45 Part 46 of the Code of Federal Regulations, regulate all research regardless of funding (with the exception of requirements for reporting information to Health and Human Services for HHS-funded research).
   
   The 2001 revision includes the adoption of the Federal Policy for the Protection of Human Subjects (the “Common Rule”) with its Subparts A, B, C and D by 16 federal agencies that conduct, support, or otherwise regulate human subjects research and laid the groundwork for the University’s policies and procedures.
3. Each of the three ethical principles of research ( i.e., the Belmont Principles) have equal moral force. However, it is recognized that, in certain circumstances, the three principles might be in conflict with one another. (For example, the principle of respect for persons suggests that the involvement of children in research be limited because they are not fully autonomous while the principle of justice suggests that children should be involved in research.) Each research project shall be considered separately and on its own merits in light of all three principles.
4. Rules derived from these Codes and ethical principles provide the foundation for the University’s policies and procedures for conducting research with human subjects. They include the following requirements:
   • The requirement to obtain informed consent.
   • The requirement to respect privacy of research subjects.
   • The requirement to use the best possible research design to maximize benefits and minimize harms.
   • The requirement to make sure that the researchers are able to perform the procedures and handle the risks entailed by the research.
   • Research that is without a favorable risk-benefit ratio will be prohibited.
   • The requirement to select subjects equitably.
   • The requirement to avoid exploitation of vulnerable populations or populations of convenience.

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Definitions and Applicability (45 CFR §46.102)

1. The Reynolda Campus of Wake Forest University has adopted the following definitions:
   
   Research means a systematic investigation (including research development, testing and evaluation) designed to contribute to generalizable knowledge.
   
   Human subject means a living individual about whom an investigator (whether
   faculty or student) conducting research obtains:
   1. data through intervention or interaction with the individual, or
   2. identifiable private information.
      • Intervention includes physical procedures by which data are gathered, and manipulation of the subject or the subject’s environment for research purposes.
      • Interaction includes observation of behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place and group discussions (e.g., focus groups), interviews, and other such settings in which data are gathered for research purposes.
      • Private information must be individually identifiable if obtaining the information is to constitute research involving human subjects.
   IRB means an Institutional Review Board established in accord with and for the purposes expressed in this policy.
   
   Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than that ordinarily encountered in everyday life or during the performance of routine physical or psychological examinations or tests.
   
   Benefit is the positive value or advantage of being part of a research study. This value may be concrete for an individual (e.g., a greater chance of having a good therapeutic outcome) or may be more intangible and general (e.g., the illumination of basic processes or causes that underlie a research topic). Compensation or inducement for study participation is not considered a benefit and shall not be considered in the balancing of risk/benefit ratios.
   
   Key personnel is defined as the principal investigator (PI) and other individuals who contribute in a substantive, measurable way to the project. Examples include but are not limited to the PI; co-investigators; the study coordinator; project personnel designing or supervising studies, administering informed consent, questionnaires or surveys or collecting data from subjects using other methods, coding data, or otherwise collecting or analyzing human subjects data.
   
   Typically, these individuals have doctoral degrees or other professional degrees, although individuals at the masters or baccalaureate level may meet this definition. The PI typically identifies the key personnel on a research project.
   
   
2. Those principles outlined in The Belmont Report, federal regulations set forth in 45 CFR §46, and in WFU policies and procedures relative to all activities which, in whole or in part, involve research with human subjects are applicable if:
   1. the research is sponsored by this institution; or
   2. the research is conducted or under the direction of any faculty, staff, student or agent of this University in connection with his or her institutional responsibilities; or
   3. the research is conducted by or under the direction of any faculty, staff, student or agent of this University, using any property or facility of the University;
   4. the research involves the use of this University’s nonpublic information to identify or contact human research subjects or prospective subjects.

   The chairperson of the Institutional Review Board (often in consultation with the Human Protections Administrator and/or full IRB) retains final judgment as to whether or not a particular activity is covered by the above.
   
   Investigators who plan to submit a protocol that would fall under the guidelines established by the Food and Drug Administration (FDA) will be referred to the IRB at Wake Forest University Health Sciences (WFUHS).

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Institutional Responsibilities

Codes of Conduct

In accordance with State and Federal regulations and the highest standard of ethical conduct, the University accepts the responsibility to reasonably ensure that, in research conducted under its auspices, the rights and welfare of human subjects are adequately protected. The University will comply with the requirements set forth in 45 CFR §46 and its Subparts B (pregnant women), C (prisoners) and D (children).

The University will encourage and promote constructive communication among research investigators, the IRB, the Office of Research and Sponsored Programs (ORSP) and human subjects to maintain a high level of awareness regarding the safeguarding of the rights and welfare of the subjects. Further, the University will assume responsibility for communicating and explaining these policies to faculty, students and other personnel and for providing procedural guidelines to effect their observance.

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Federalwide Assurance (45 CFR §46.103)

Wake Forest University – Reynolda Campus faculty, staff and students who comprise its schools, departments, divisions and facilities are subject to a Federalwide Assurance (FWA) for the Protection of Human Subjects with the Office for Human Research Protections (OHRP) of the US Department of Health and Human Services (DHHS) and this policy. The assurance formalizes the University’s commitment to protect human subjects in research conducted under its auspices.

The University’s FWA number is: FWA 00001732.
The IRB Registration number is: IRB00000435
The Organization number for WFU is: IORG0000259.

The FWA is renewable every five years, upon penalty of restriction, suspension or
termination of the FWA. Both the FWA and registration of the University’s IRB,
required under the OHRP Federalwide Assurance, are maintained in the Office of
Research and Sponsored Programs.

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Establishment of an Institutional Review Board

1. The University will establish one (1) Institutional Review Board (IRB) to review all human subjects research conducted on the Reynolda Campus. Research conducted at Wake Forest University Health Sciences (WFUHS) is subject to review by WFUHS’s IRB.
2. Research reviewed and approved by the IRB may be subject to review and disapproval by University officials; however, University officials may not approve research previously disapproved by its IRB. (45 CFR §46.112)
3. The University will work with the IRB in the development of policies and procedures for effective and efficient administration of the human subjects protection program. (45 CFR §46.103(b)(4))
4. To facilitate and promote the work of the IRB, the University will provide resources including, but not limited to, sufficient staff and meeting space to support the IRB’s review and recordkeeping duties. (45 CFR §46.103(b)(2))
5. The University will provide training and educational opportunities for the IRB, investigators, professional and support staff supporting the IRB.
6. The University will ensure that its Institutional Review Board is constituted by members who are sufficiently qualified and able to ascertain the acceptability of research in terms of the applicable laws, regulations, and University policies and procedures. (45 CFR §46.103(b)(3))
7. The University has the responsibility to provide adequate resources to allow the IRB to meet its Federal and University mandates.

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Administrative Oversight

1. Authorized Institutional Official. Safeguarding the rights and welfare of human subjects in research is a general institutional policy delegated by the President through the Interim Provost. It is their responsibility to exercise appropriate administrative oversight to ensure that Wake Forest University’s policies and procedures, designed to protect the rights and welfare of human subjects, are effectively applied in compliance with its Assurance. (45 CFR §46.103(c))
2. Human Protections Administrator (HPA). The Associate Director for Faculty Research Compliance and Support, Office of Research and Sponsored Programs (ORSP), shall be the designated Human Protections Administrator (HPA) responsible for compliance with Federal regulations and University policy. (45 CFR §46.103(c)) The HPA or a designee shall prepare and maintain adequate documentation of IRB activities, in accordance with 45 CFR §46.115, including the following:
   1. Ensure that the Federalwide Assurance and IRB Registration are current and filed in a timely fashion with the Department of Health and Human Services through the Office of Human Research Protection.
   2. Process all research protocol applications and any subsequent safety events, amendment requests, continuing reviews and study closures involving human subjects in a timely manner. Communicate the outcomes of reviewed research to investigators and university officials in a timely manner. (45 CFR §46.103(b)(4))
   3. Meeting agendas. Prepare an agenda and distribute it at least one weeks prior to the IRB meeting.
   4. Keep minutes of IRB meetings in sufficient detail to record the following information: Attendance at each meeting, actions taken by the IRB, the vote on actions taken, the basis for requiring any changes in or disapproving research, determinations regarding risk and approval period (review interval), a written summary of the discussion of controverted issues and their resolution, and any other housekeeping decisions made. (45 CFR §46.115(a)(2))
   5. Maintain a current list of IRB members with credentials, department affiliation and relationship to WFU. (45 CFR §46.103(b)(3))
      • Name
      • Earned degrees
      • Representative capacity
      • Experience (board certifications or licenses) sufficient to described anticipated contributions to IRB deliberations
      • Any employment or other relationship between each member and the institution (e.g., full-time, part-time employee, consultant, University board member).
      • Term of service
      • Phone number and email address
   6. Monitor mandatory human subjects education certification/recertification of IRB members, PIs and other personnel as required.
   7. Make available the following resources: The Declaration of Helsinki, the Nuremberg Code, the Common Rule and HHS Regulations, The Belmont Report, Wake Forest University – Reynolda Campus Institutional Review Board Policies and Procedures, Investigator’s Guide to Human Subjects Research, User's Guide to eIRB, current Federalwide Assurance and IRB Registration.
   8. Maintain and publish written procedures and policies of the University, its IRB (45 CFR §46.103(b)(4) and (5)), the principal investigator, and ORSP, the institution’s Federalwide Assurance and IRB Registration.
   9. Maintain a web site which includes information about the IRB, its membership, meeting dates, instructions and forms, and policies and procedures.
   10. Maintain IRB records pertaining to research for three (3) years after completion of the research. All records must be accessible for inspection and copying by authorized persons at a reasonable time and in a reasonable manner. Copies of information about all submissions, correspondence and other communication regarding the study should be filed in reverse chronological order. The information should include, but is not limited to, the following: original IRB research protocols, reviewer’s comments and IRB action, committee action letters, revised IRB protocols, final approval letters, adverse event reports, serious or continuing noncompliance by investigators, injuries to subjects, unanticipated problems, amendments, related correspondence, copies of IRB approvals from collaborating institutions or performance sites, letters of cooperation from performance sites, electronic mail correspondence directly impacting a protocol review/change, and protocols for continuing review, closure or termination. (45 CFR §46.115)
   11. Keep the IRB informed of the status of all research protocols. (45 CFR §46.103(b)(5))
   12. Provide statement to subjects as required by 45 CFR §46.116(b)(5) of significant new findings developed in the course of the research which may relate to the subject’s willingness to continue participation.
   13. Conduct quarterly random and/or targeted monitoring and oversight.
       
       The HPA may conduct procedural and recordkeeping audits to detect, correct and report, as necessary, administrative and/or material breaches in protecting the rights and welfare of human subjects, as required by federal regulations and/or University policy. (45 CFR §46.103(b)(5))

       In response to an IRB directive to monitor approved research projects, the HPA may conduct targeted audits of research procedures by requesting progress reports from PIs, examining informed consent documents, viewing research materials (other than confidential data) and/or verifying from sources other than the PIs (e.g., research investigators or department chairs) that no material changes in the study have occurred that have not been approved by the IRB (criteria and mechanisms used to make these latter determinations shall include either randomly selected projects, or non-random selection of:

       1. complex projects involving unusual levels or types of risk to subjects,
       2. projects conducted by investigators who previously have failed to comply with federal regulations or IRB determinations, or
       3. projects where concern about possible material changes occurring without IRB approval have been raised based upon information provided in continuing review reports or from other sources.).

       
       These audits allow for the early identification and correction of any problems. The HPA will inform the PIs of the audit and the audit’s outcomes in a timely manner. If deemed necessary, the HPA will report the outcomes of the audit to the IRB chair and/or the Interim Provost and will make recommendations concerning actions to be taken in light of any material violations of protocol.

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The Institutional Review Board (IRB)

To fulfill its responsibility to protect the rights and welfare of human subjects in research, the University authorizes the IRB to review, approve, require modifications, suspend, disapprove or terminate all research involving human subjects conducted under the auspices of the University (45 CFR §46.19). This includes investigating, reviewing and determining all issues of serious or continuing noncompliance with 45 CFR §46 or IRB policy within a reasonable timeframe and with a corrective plan. See also Noncompliance.

The IRB shall evaluate research in light of the ethical principles set forth in The Belmont Report and codified by Title 45 CFR §46, including its subparts. The primary responsibilities of the IRB include, but are not limited to, the following:

• Ensure that privacy of subjects is protected and confidentiality maintained.
• Ensure that informed consent is sought in language understandable to subjects and obtained under conditions that minimize the possibility of coercion or undue influence.
• Ensure that research includes appropriate safeguards to protect the rights and welfare of all research subjects.
• Ensure that appropriate safeguards are taken when research subjects are members of vulnerable categories or when the research involves greater than minimal risk.

The responsibilities of the IRB endure regardless of the IRB’s geographical location relative to the research.

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Committee Membership

Wake Forest University (WFU) has established its IRB membership requirements in accordance with the compositional requirements of 45 CFR §46.107.

1. Invitation. After consultation with appropriate department chairs, invitation to membership on the IRB shall be extended in writing by the Interim Provost.
2. Composition (45 CFR §46.107)
   1. The IRB shall have at least five members with varying backgrounds to promote complete and adequate review of research activities conducted by the institution. (45 CFR §46.107(d)) (Members shall be drawn from departments actively involved in research with human subjects whenever possible. The IRB chair and HPA shall determine department participation and send their recommendations for Board membership to the Interim Research.
   2. IRB members shall include at least one scientist, one non-scientist (45 CFR §46.107(c)) and one un-affiliated member drawn from the local community-at-large and without direct ties to the university or part of an immediate family affiliated with the university. (45 CFR §46.107(d))
   3. The IRB membership shall be composed of faculty who are qualified through maturity, experience, expertise and sensitivity to such issues as community attitudes to assure complete and adequate review of activities commonly conducted by the institution, and to ensure respect for its advice and counsel for safeguarding the rights and welfare of human subjects. Every effort will be made to ensure that the IRB is racially and culturally diverse, and consists of both male and female members, but selection should not be made purely on these bases. (45 CFR §46.107(a)(b) and (d))
   4. IRB members must possess the professional competence necessary to ascertain the acceptability of protocols in terms of institutional commitments, and regulations, applicable laws, standards of professional conduct and practice, and community attitudes. (45 CFR §46.107(a))
   5. If the IRB routinely reviews research that involves a vulnerable class of subjects, it must include an expert who has experience working with this population. (45 CFR §46.107(a))
   6. The IRB may, at its discretion, invite individuals with competence in special areas to assist in the review of a research application (see also Cross-Cultural Research). (45 CFR §46.107(f)) In addition, the IRB may invite the principal investigator (PI) of a research protocol to attend the meeting in which the proposal is discussed. However, these invited persons may not vote; the PI may neither vote nor be present during the Board discussion or vote concerning his or her proposal.
   7. The WFU IRB cannot review prisoner research because its membership does not include a prisoner or prisoner representative with appropriate background and experience to serve in that capacity unless another IRB with the required prisoner representation will also be reviewing the research (45 CFR §46.304(b)). The HPA will assist PIs in finding an outside IRB to review the research and in complying with the applicable regulation.
3. Responsibilities of IRB Members
   1. IRB members:
      • shall be appointed to the IRB by the Interim Provost for overlapping three-year terms and may not serve for more than two consecutive terms without a minimum of one year off the Board. Approximately 1/3 of the members should rotate off the IRB each year.
      • shall serve at the pleasure of the Interim Provost and may be reappointed at the conclusion of their term. Removal by the Interim Provost may be effected at any time, given written notice, for due cause (e.g., failure to meet IRB responsibilities, chronic lack of attendance, failure to meet educational requirements for human subject research, ethical misconduct, disregard for federal regulations or University policies).
      • shall maintain an understanding of the ethical principles of human subject research, federal regulations, applicable state laws, the University’s Assurance and institutional policies and procedures for the protection of human subjects.
      • shall keep in strict confidence all information related to the research as well as discussion during or after meetings.
      • shall complete the CITI human subjects research and IRB member courses.
      • shall complete OHRP's Assurances tutorial.
      • shall prepare for and attend all scheduled IRB meetings and training, unless other arrangements have been made at the time of appointment.
      • shall notify the HPA as soon as possible when an alternate will attend an upcoming meeting and shall work with the alternate to help prepare him or her for the meeting.
      • shall notify the HPA when he or she will take a leave of absence of at least 4 months and will not participate in IRB meetings so that a replacement can be appointed as a regular voting member.
      • shall serve as a reviewer on a rotating basis with other IRB members.
      • may be asked to serve as primary reviewers for full board and expedited protocols. Primary reviewers are responsible for ensuring that assigned protocols undergo a substantive and meaningful review. In addition, primary reviewers will lead the discussion at the convened meeting and submit their comments/concerns regarding their review via eIRB.
      • shall not vote nor participate in the review or continuing review of any project when he or she has an apparent or real conflict of interest, except to provide information requested by the IRB, and shall notify ORSP when he or she has a conflict of interest. (45 CFR §46.107(e))
   2. IRB Chairperson

      Selection of the chairperson. The IRB chair should be a highly respected individual from within the institution who is knowledgeable about human subject protection regulations, and fully capable of managing the IRB and the matters brought before it with fairness and impartiality. He or she must be perceived as fair and impartial, immune from pressure either by the institution’s administration, the investigators whose protocols are brought before it, or other professional or nonprofessional sources. The task of making the IRB a respected part of the institutional community falls primarily on the shoulders of the Chair.
      
      The IRB chair shall be a voting member chosen from among senior members of the committee. Appointments to the IRB should allow for a rotation of chairpersons across research-oriented departments. The chair shall be appointed by the Interim Provost to serve a one-year term.

      Responsibilities of the chair. The IRB chair shall meet the responsibilities of an IRB member. In addition, the IRB chair:

      • shall ensure that the IRB fulfills its responsibilities and operates in a fair and impartial manner;
      • shall plan and facilitate IRB meetings;
      • shall review and approve or disapprove in a timely manner, as appropriate, any resubmissions of protocols of provisionally approved protocols by the full IRB only when the convened IRB has stipulated specific revisions to address minor concerns;
      • shall serve as mediator when any unresolved discussion arises between the investigator and the IRB or among IRB members;
      • shall attend training conferences (PRIM&R) annually at the ORSP’s expense (optional).
      • Although not mandatory, the chair should be available to serve on the IRB a minimum of one year after his or her term as chair.
4. The Interim Provost may appoint a Vice-Chair for the IRB who will serve as a backup for the chair, upon request from the IRB chair or the HPA. He or she should meet the same requirements as the Chair and should be capable of fulfilling the same responsibilities as the Chair.
5. An alternate member(s) may be designated, as needed, for a regular voting member(s). The appointment of an alternate member shall be based on expertise similar to that of the regular voting member(s). An alternate member may vote only when the regular voting member is absent.

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IRB Meetings (45 CFR §46.108(b))

1. The IRB shall meet at regularly scheduled intervals to discuss submitted protocols and reach a decision on each submission. A schedule of IRB meetings is established by the HPA in consultation with the IRB chair and is published annually.
2. Convened meetings
   1. The IRB observes the following requirements for convened meetings: A majority of the members of the IRB must be present including at least one scientist and one nonscientist. If the required number of members is lost during a meeting, no further action may be taken until it is restored. In order for research to be approved, it must receive the approval of a majority of those voting members present at the meeting.
   2. A convened meeting may be conducted by telephone conference call, provided that each participating IRB member has access to all pertinent material prior to the meeting and can actively and equally participate in the discussion of all protocols. Minutes of such meetings must clearly document which members were present via conference call, and that all had access to relevant material prior to the meeting and could fully participate in the discussion.
3. The HPA and IRB chair may call the IRB into special meetings outside the published schedule of meetings. If the IRB is appropriately constituted at such special meetings, it may review and act on IRB protocols and conduct any other business.
4. Minutes of IRB meetings shall include attendance at meetings; actions taken by the IRB; vote on these actions including the number of members voting for, against, recusing, and abstaining; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution.

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Education and Training

Mandatory Certification

1. All investigators and key personnel involved in research with human subjects must complete mandatory CITI (Collaborative IRB Training Initiative) training prior to beginning their research. Researchers are required to complete the basic CITI program that correlates with the type of research they are doing. Researchers who need to be recertified complete the refresher course. A score of 80% correct is required to receive credit for the course.
   
   All key personnel on the project must complete the training and the PI will ensure that granting agency requirements in this regard are met.
   
   Researchers should complete the basic CITI program that best correlates with the type of research proposed: Group 1 Social/Humanistic/Behavioral Research program for graduate and undergraduate students, faculty and staff; Group 2 Social/Humanistic/Behavioral Research program for graduate and undergraduate education students, faculty and staff; or Group 3 Biomedical Research for graduate and undergraduate students, faculty and staff. In addition, those involved with international research, internet-based research and/or vulnerable subjects are required to complete the additional topical modules.
2. Those key personnel who have completed training elsewhere may submit documentation of completion to the HPA. The Interim Provost determines whether or not the training satisfies the requirements of Wake Forest University.
3. The IRB may require that additional project personnel receive educational training as a prerequisite for project approval if it deems this necessary to ensure the welfare of the subjects.
4. IRB members and ORSP staff supporting the IRB are required to complete CITI training and OHRP’s Assurances tutorial.
5. The Interim Provost may make changes in these education and training requirements, as appropriate. PIs should contact the HPA or the Interim Provost for Research to obtain updated and complete information about requirements for mandatory education.

Recertification and Ongoing Education

1. Ongoing training will be provided to IRB members by the HPA and may include such topics as changes in federal regulations, review of the responsibilities and obligations of committee members with regard to the protection of human subjects.
2. Recertification for PIs and other key personnel will be required at five-year intervals for groups 1 and 2; group 3 requires recertification every 3 years. Those requiring recertification must take the refresher course. The Interim Provost shall make decisions concerning the content requirements for certification and recertification.
3. The ORSP will notify faculty members at least two months prior to the expiration of their certification.

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IRB Records (45 CFR §46.115)

Adequate documentation of IRB activities shall be prepared and maintained and shall include the following:

1. Research proposals reviewed, approved consent and assent documents, amendment requests, continuing review applications, safety events and other research-related documents as needed.
2. Minutes of IRB meetings which 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, recusing, and abstaining; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution.
3. Records of continuing review activities.
4. Correspondence between the IRB and the investigators.
5. A list of IRB members in the same detail as described in 45 CFR §46.103(b)(3).
6. Written procedures for the IRB in the same detail as described in 45 CFR §46.103(b)(4) and (5).
7. Statements of significant new findings provided to subjects as required by 45 CFR §46.103(b)(5).

Records required by 45 CFR §46 shall be retained for at least 3 years. Records relating to research shall be retained until no longer scientifically useful or for 3 years after completion of the research, whichever is longer. All records shall be accessible for inspection and copying by authorized representatives at reasonable times and in a reasonable manner.

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The Investigator’s Responsibilities

In accordance with the provisions of Wake Forest University FWA, research investigators who conduct human subjects research under the auspices of the University (faculty, staff, students, and affiliated researchers), acknowledge and must accept their responsibility for protecting the rights and welfare of human subjects in research. (45 CFR §46.101(b)(1)-(6), 109(e), 118 and 119)

Safeguarding the well-being of and information about an individual is a primary responsibility of the investigator. The investigator acknowledges and accepts his or her responsibility to protect the rights and welfare of human research subjects, and for complying with all applicable regulations and educational requirements.

When the investigator is a student, responsibility for the conduct of the research, and for the welfare and supervision of human subjects lies with both the student and the faculty advisor. All student research must be overseen by a faculty advisor. Faculty advisors assume the role of principal investigator and must complete the mandatory human subjects protection education. Faculty advisors must review, approve and submit all protocols on behalf of student co-investigators under their supervision; and supervise students in all aspects of the conduct of research: recruitment, data collection, data entry and analysis, secure storage and destruction of data, and presentation of findings.

The investigator and study team shall prepare the IRB application that contains all required information and documentation including a protocol document that includes a description of the research, background and rationale; biosketches; informed consent and, if applicable, assent documents and copies of all other relevant information and documentation (questionnaires, test instruments, recruitment tools, scripts, debriefing statements, contact letters, approval memos, etc.). During the review process, the investigator must respond to IRB concerns within 30 days (for exempt or expedited protocols) or 60 days (for full board review protocols) or the application will be administratively withdrawn.

All research records and correspondence are to be retained in a manner approved by the IRB, and kept in a secure location by the investigator for as long as the research data remains scientifically valid or for a period which meets departmental or sponsor requirements before being destroyed.

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The Institutional Review Board (IRB) and the Review Process

Scope of Review

IRB review and approval shall be required for any research involving human subjects that is conducted by or under the direction of Wake Forest University faculty, staff, or students in connection with the fulfillment of institutional responsibilities or academic requirements; or is performed with or involves the use of University records, facilities or equipment belonging to the University.

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The IRB and the Review Process (45 CFR §46.109)

1. The IRB chair or designee shall determine whether a given activity can be considered human subjects research.
2. Certain categories of research involving minimal risk to subjects and meeting one of the Federal categories for expedited review need not be reviewed and approved by the full IRB, but rather by the IRB chair or a duly authorized designee through expedited review procedures.
3. The three basic ethical principles – Respect for Persons, Beneficence, and Justice – set forth in the Common Rule and The Belmont Report, shall guide the IRB in its review.
   1. Respect for Persons
      1. Where appropriate, the IRB shall require adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
      2. In accordance with 45 CFR §46.111(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, the IRB shall determine whether additional safeguards have been included in the research to protect the rights and welfare of these subjects.
      3. The investigator shall seek informed consent from each prospective subject or the subject’s legally authorized representative in accordance with and to the extent required by 45 CFR §46.116, and such consent shall be appropriately documented, in accordance with, and to the extent required by 45 CFR §46.117 and retained as a matter of record.
      4. When research involves more than minimal risk or substantial stress or discomfort, such risk, stress or discomfort shall be carefully explained to the subject before his or her participation and justified by the expected benefits of the research.
      5. A subject shall have the right to withdraw from a research project at any time or to refuse to participate without loss of benefits to which the individual would otherwise be entitled. In addition, a subject shall have the right to appropriate professional care, to privacy and confidentiality in the use of personal information, and to freedom from undue embarrassment, discomfort, anxiety and harassment.
   2. Beneficence
      1. Direct or potential benefits to the subject or the importance of knowledge to be gained shall not preclude consideration of the inherent risks to the individual.
      2. The IRB will consider the qualifications of the investigator, his or her professional development, and experience when assessing the degree of risk to subjects in the research project. Protocols which require skill levels beyond those held by the PI will be disapproved or modified. The PI may also be required to include additional qualified personnel in the project. These considerations apply to research that may fall within all categories of IRB review.
      3. Where appropriate, research plans shall make adequate provision for monitoring the data collected to ensure the safety of subjects.
      4. Risks to subjects shall be minimized:
         1. by using procedures that are consistent with sound research design and do not unnecessarily expose subjects to risks, and
         2. whenever appropriate by using procedures already being performed on the subjects for diagnostic or treatment purposes.
      5. Risks to subjects shall be reasonable in relation to anticipated benefits, if any, to subjects, and the importance of knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB shall consider only those risks and benefits that may result from the research (as distinguished from risks and benefits subjects would receive even if they were not participating in the research). The IRB shall not consider the long-range effects of applying knowledge gained in the research as among those research risks that fall within the purview of its responsibilities.
   3. Justice
      1. Selection of subjects shall be equitable. When appropriate, every effort will be made to include subjects of diverse age, race, gender, and ethnicity.
      2. The IRB shall ensure that compensation or inducement offered for participation in a study is made appropriately, with subjects fairly recruited and adequately informed rather than unduly influenced by promised compensation. Financial remuneration or other inducements should not be so great as to be coercive to potential subjects and should constitute reasonable compensation for the inconvenience of participating. Compensation or inducement information shall be included in the Informed Consent.
      3. No recruitment or involvement of human subjects in research shall be permitted until the IRB has reviewed and approved the research application, and informed consent has been obtained. It shall be the investigator’s responsibility to obtain approval from the IRB prior to the initiation of any research, including pilot or pre-test studies, involving the use of human subjects. Non-affiliated researchers seeking to recruit on the WFU campus shall submit a brief description of the proposed study and a copy of the study’s approval letter from their institution’s IRB. If the HPA determines the University is not engaged in the research, he/she shall forward the request to the appropriate University officials for their consideration.
      4. The investigator should ensure that consent for participation is sought only under circumstances that minimize the possibility of coercion or undue influence.
         1. When using students as subjects, the investigator should ensure that the consent for participation is sought only under circumstances that minimize the possibility of coercion or undue influence. If participation in the research is in partial fulfillment of a course requirement, the research option must be included in the original course syllabus and genuine equivalent alternatives to participation must be available (e.g., term papers, literature review, attendance at colloquia or research seminars). Participation must be voluntary so the student can withdraw at any time without penalty and still receive appropriate credit to the level of his or her participation. When a research project requires attendance in multiple sessions, a subject may withdraw from the study at any time and receive credit for the sessions he or she has attended.
         2. When employees are involved in research, the researcher must be able to provide justification other than convenience for their involvement.

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IRB Responsibilities

1. The IRB shall follow the written policies and procedures of Wake Forest University for the protection of human subjects in research. These policies and procedures shall be in compliance with Federal regulations and State law. (45 CFR §46.108(a))
2. The IRB shall adopt appropriate procedures to implement these policies with the advice and counsel of the ORSP.
3. The IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities covered by this policy. (45 CFR §46.109(a))
4. Except when an expedited review procedure is applicable, the IRB shall review proposed research at convened meetings at which a majority of the members are present, including at least one member whose primary concern is in a non-scientific area. To be approved, research shall receive the approval of a majority of those members present at the meeting. If the required number of members is lost during a meeting or a non-scientist is not present, any IRB action or vote taken at this time shall be considered invalid. (45 CFR §46.108(b))
5. The IRB shall require that information given to subjects as part of the informed consent process is in accordance with 45 CFR §46.116. The IRB may require that information, in addition to those required elements specified in 45 CFR §46.116(a), be given to subjects when in the IRB’s judgment the information would meaningfully add to the protection of the rights and welfare of the subject.
6. The IRB shall require documentation of informed consent or may waive documentation in accordance with 45 CFR §46.117.
7. The IRB, through the HPA shall notify investigators 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 disapproves or requests modifications to the research activity, it shall include in its written notification a statement of the reasons for its decision and shall give the investigator an opportunity to respond in writing. (45 CFR §46.109(d)) See also Appealing an IRB Decision.
8. The IRB may request that the HPA conduct targeted audits to assess compliance with local, state and federal regulations, subject safety and IRB policies and procedures when it determines the need for additional supervision or participation by the IRB during the initial and continuing review or as new information is presented by the PI. When the audit report is received, the IRB may accept it with or without revisions, impose additional measures for subject’s safety (e.g., request status reports after each subject intervention), decrease the continuing review cycle, conduct a follow-up audit, require oversight/signatures by superior on all research, replace the PI by a qualified investigator who is not subordinate to the investigator being replaced, or limit the PI’s ability to submit new research studies to the IRB.
9. Certification of IRB review and approval for all Federally-sponsored research involving human subjects shall be submitted to the ORSP for forwarding to the appropriate Federal department or agency, as required. Compliance will occur within the time and manner prescribed for forwarding certifications or IRB review to DHHS or other Federal department or agency. (45 CFR §46.103(f))

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Levels of Review

Research projects shall be reviewed at one of three levels, depending on the IRB Chair’s interpretation of the project’s risk to the human subjects, in line with the Federal guidelines that define the categories of review.

Research means a systematic investigation, including research development, testing and evaluation designed to contribute to generalizable knowledge. Class research demonstrations and projects that are not intended to contribute to generalizable knowledge are not required to be reviewed by the IRB. Results generated by such projects should not be published or presented in a public forum.

Regular courses, research methods courses, and even service-learning components of courses that use individual or group projects that engage people from outside that particular class may need IRB approval. Any of the following conditions requires IRB review:
* If the interaction with people involves record keeping (e.g., field notes, survey responses) that will be stored and may be used in future for publications by the student(s) or professor.
* If any part of the work will be presented orally or in print to any audience larger than the enrollment of that particular class. This includes honors thesis presented to or available to non-class members.

The following requires IRB review or evaluation by a departmental committee that reports to the IRB:
* If the activity is entirely pedagogical, does not meet the definition of research (the gathering of evidence to report such findings to anyone outside the classroom), but carries unusual risks such as:
* observations of or interviews of people on illegal or unusually sensitive subjects (e.g., immigrant status; drugs; pornography);
* deceptions, by having students present themselves to non-class members as something they are not;
* norm violations, having the students transgress the norms of a group
in order to observe the group’s response (e.g., having students pose as same-sex couples at a church activity where the said church forbids homosexuality;
* ventures into risky venues (e.g., events sponsored by hate groups such as the KKK).

When all or many students in a research class will conduct similar projects, the instructor may submit a single IRB application giving a general description of the aims of the class project (e.g., different datasets or types of interactions with subjects) and any other factors that would explain the project to the IRB.

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Exempt Research

1. Exempt research is not subject to IRB federal regulations and does not require informed consent.
2. Federal human subjects protection regulations define the following six categories of human subjects research as exempt (45 CFR §46.101(b)). All six categories apply to children, category 2 with a caveat.
   
   Children are defined as persons who have not attained the legal age for consent to procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted. In North Carolina, residents under 18 years of age are considered children unless they are “emancipated” by court order or marriage or are in the military. See also Children in Research Involving Human Subjects.
   
   
   1. Category 1: Research conducted in established or commonly accepted educational settings, involving normal education practices, such as (a) research on regular and special education instructional strategies or (b) research on the effectiveness of or the comparison among instructional techniques, curricula or classroom management methods.

   This category applies to children and allows exemption for research studies that involve evaluation of normal educational practices conducted in commonly accepted educational settings. Children, as well as adults, may be subjects of such studies. Commonly accepted settings are not limited to schools. A car may be a commonly accepted setting for a driver education program. A clinic may be a commonly accepted setting for a medical student or resident education program. A repair facility may be a commonly accepted setting for a technician education program. PIs must provide evidence that the educational practices to be studied are frequently used educational practices carried out in a place where such practices are commonly accepted for this exempt category to apply.

   2. Cateory 2: Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior unless: (a) information obtained is recorded in such a manner that human subjects can be identified directly or indirectly through identifiers linked to the subjects; and (b) 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.

      This category is applicable to children; however, for research involving survey or interview procedures or observations of public behavior, the exemption does not apply except for research involving observation of public behavior when the investigator(s) do not participate in the activities being observed.

   3. Category 3: Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if: (i) the human subjects are elected or appointed public officials or candidates for public office; or (ii) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.
   4. Category 4: Research involving the collection or study of existing data, documents, records, pathological specimen, 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. Category 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: (a) public benefit or service programs; (b) possible changes in or alternatives to those programs or procedures; or (c) possible changes in methods or levels of compensation or inducement for benefits or services under those programs.
   6. Category 6: Taste and food quality evaluation and consumer acceptance studies, (a) if wholesome foods without additives are consumed or (b) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the US Department of Agriculture.
3. If the investigator makes any substantive changes to the project which might change its designation, he or she must notify the IRB who will determine whether the research is still exempt or must receive additional review.
4. Exempt research is subject to continuing review every three years.

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Expedited Research (45 CFR §46.110)

Expedited review categories of research shall comply with “Categories of Research That May Be Reviewed by the IRB through an Expedited Review Procedure”. 63 FR 60364-60367, November 9, 1998.

1. The only other research for which an IRB may use an expedited review procedure is that which involves no more than minimal risk to the subjects and in which the only involvement of human subjects will be in one or more of the following categories. The activities should not be deemed to be of minimal risk simply because the activity is included on this list.
   1. Research involving materials (data, documents, records or specimens) that have been collected, or will be collected solely for non-research purposes.
   2. Collection of data from voice, video, digital, or image recordings made for research purposes.
   3. 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 assurances methodologies.
   4. Continuing review of research previously approved by the convened IRB as follows: (a) where (1) the research is permanently closed to the enrollment of new subjects; (2) all subjects have completed all research-related interventions; and (3) 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 of records that are not anonymous (i.e., contain identifiers).
2. The eligibility of some research for review through the expedited procedures is in no way intended to negate or modify the policies of this institution or the other requirements of 45 CFR §46.
3. The IRB may use the expedited review procedures to review minor changes in previously approved research during the period for which approval is authorized.
4. Expedited review is carried out by an IRB member.
5. In reviewing the research, reviewers may exercise all of the authorities of the IRB except the reviewers may not disapprove the research. Disapproval of a research application requires the majority of the full IRB. Reviewers may recommend that a disapproved expedited review go to the full board for review.
6. At a convened IRB meeting, any member may request that an activity which has been approved under the expedited procedure be approved by the IRB in accordance with full board review procedures. A vote of the members shall be taken concerning the request and the majority shall decide the issue. A PI may also request that an application receive full board review.
7. Amendments for previously approved research may be approved under an expedited review procedure.

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Research for Which Full Board Review Is Required

1. The IRB may require full review of any research submitted or approved under expedited review and any research not approved by expedited review.
2. The primary criterion for full board review is the risk to subjects, including not only the procedures followed but the interaction between research procedures and the populations being studied.
3. Examples of research activities that must be reviewed by the full IRB include:
   1. Research in which potential subjects may not be given sufficient information to make decisions about whether to participate and accept potential risks. This may include research in which outright deception or incomplete disclosure of the purpose of the study might reasonably affect a person’s decision to participate in the study.
   2. Research involving more than minimal risk, where defined as “the probability and magnitude of harm or discomfort are not greater in and of themselves than those ordinarily encountered in the daily life or during the performance of routine physical or psychological examinations or tests”.
   3. Non-curricular, interactive research in primary and secondary schools.
   4. Research in which participation per se in the study constitutes a risk (e.g., identification as a subject in a drug-use survey). This would include research in which researchers have applied for a waiver of documentation of consent, which can be used as a method of reducing risks to subjects who may be placed at risk simply by being involved in the study.
   5. Some research involving special populations, e.g., children, pregnant women and mentally incompetent persons.
   6. Research involving potential risks to subject’s right to privacy and/or threats to confidentiality.

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Procedures for IRB Review of Research

1. When IRB protocols are reviewed by the full board, related continuing review and amendment requests and safety event reports shall continue to be reviewed by all members of the committee prior to the meeting.
2. A majority of the IRB constitutes a quorum and is required in order to convene a meeting for the review of research protocols. At least one non-scientist and one scientist must be present at the convened meeting before the IRB can conduct its review of research.
3. Before a research application can be approved, it must receive the approval of the majority of those voting members present at the convened meeting.
4. The IRB will make one of four determinations regarding an application:
   1. Forward for approval without questions, concerns or requests for modifications.
   2. Provisional approval. The research activity may not be undertaken until the IRB’s concerns are addressed and submitted to the designated IRB member for review and approval.
   3. Postpone. This action is used if quorum is lost and therefore, review of the application cannot proceed. The application returns to administrator review and will be rescheduled for the next meeting.
   4. Table. This indicates approval by the IRB has been withheld as substantive concerns or significant requests for clarification have been raised and/or the proposed research does not meet University or Federal guidelines for the protection of human subjects. The research activity may not be undertaken until the IRB’s concerns are addressed and submitted to the full IRB for review and approval.
   5. Disapprove. The IRB may disapprove a proposed activity with serious and substantive problems and/or that fails to meet University or Federal guidelines for the protection of human subjects.
5. Approval of the proposed research is usually granted for a period of one year commencing on the date of the convened meeting of the IRB at which the protocol was reviewed and approved. Based upon an assessment of the degree of risk to human subjects or of protocols with a high risk to potential benefit ratio, the IRB may specify special conditions whereby the investigator has a shorter approval period or must report research progress at specific intervals.
6. Investigators will be notified via eIRB of the IRB’s decisions in accordance with 45 CFR §46.109(d), within 24 hours of the convened meeting.
7. Criteria for IRB approval of research include the following:
   1. Risks to subjects are minimized by using procedures that are consistent with sound research design and do not unnecessarily expose subjects to risk.
   2. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result from the research.
   3. Selection of subjects should be conducted in an equitable manner and recruitment procedures should be free of coercion.
   4. The proposed research considers the privacy rights of subjects and protects their confidentiality.
      
      Privacy refers primarily to the methods used to obtain information about subjects; confidentiality to the methods used to ensure that information obtained by investigators is not improperly divulged.
      1. The IRB must ensure that the researcher has made adequate provision to protect the privacy of subjects by considering:
         • the private nature of any information sought
         • the likelihood that subjects would consider the release of information as an invasion of privacy
         • the importance of the research
         • the availability of alternative ways to conduct the study
      2. Because IRB approval must be secured when a researcher wishes to access existing records to identify subjects for participation in a study and will record subjects’ names or use other methods of identification for follow-up, the Board must determine if subjects’ consent must be secured by considering the following:
         • the sensitivity of the information to be reviewed
         • the vulnerability of the subject population
         • the purpose for which the investigator wants access to the information
      3. Special Populations. When some or all of the subjects are likely to be vulnerable to coercion or undue influence (such as children, pregnant women, handicapped or mentally disabled persons, or economically or educationally disadvantaged persons), additional safeguards must be included in the study to protect the rights and welfare of these subjects. (§46 CFR 46(Subparts B, C, D))
   5. The IRB must ensure that appropriate procedures are included to protect the confidentiality of the study data and subjects’ identities. Researchers are encouraged to apply for “Certificates of Confidentiality”, which protect investigators against compelled disclosure of identifying information about subjects, under the Public Health Service Act of 301(d), 42 USC §241(d) when research is especially sensitive and confidentiality cannot be guaranteed. See the Investigator’s Guide for more information.
   6. Review and approval of research requires that the investigator follow the procedures and policies laid out in this document.

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Informed Consent Process

Informed consent must be sought from each prospective subject or the subject’s legally authorized representative before research is begun. Consent is a continuing process and subjects always retain the right to withdraw from participation in a research project. Federal policy requires that investigators inform subjects of any important new information that might affect their willingness to continue participating in the research.

1. The basic elements of the informed consent (45 §46.116) are:
   1. A statement that the study involves research. (45 §46.116(a)(1))
   2. An explanation of the purpose of the research. (45 §46.116(a)(1))
   3. The expected duration of the participation. (45 §46.116(a)(1))
   4. A description of the procedures to be followed and, if appropriate, identification of any procedures that are experimental (e.g., therapies that are being tested). (45 §46.116(a)(1))
   5. A description of any reasonably foreseeable risks or discomforts to the subject. (45 §46.116(a)(2))
   6. A description of any benefits to the subjects or to others which may reasonably be expected from the research and how that will contribute to the field of study or may benefit others. (45 §46.116(a)(3))
   7. A disclosure of appropriate alternative procedures or courses of treatment, if any, that may be advantageous to the subject, description of foreseeable risks or discomforts to the subject. (45 §46.116(a)(4))
   8. A statement describing the extent, if any, to which confidentiality of records identifying the subject is maintained. This includes the matter and place of data storage. (45 §46.116(a)(5))
   9. For research involving more than minimal risk, an explanation as to whether any compensation is available, and an explanation as to whether any medical treatments are available if injury occurs and what they consist of or where further information may be obtained. (45 §46.116(a)(6))
   10. An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury. (45 §46.116(a)(7)) (WFU consent forms should include the address, phone number and email addresses for the PI and the ORSP.)
   11. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled. (45 §46.116(a)(8))
2. Additional requirements may include:
   1. A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant), which are currently unforeseeable. (45 §46.116(b)(1))
   2. Anticipated circumstances under which participation may be terminated by the investigator without regard to the subject’s consent. (45 §46.116(b)(2))
   3. Any additional costs to the subject that may result from participation in the research. (45 §46.116(b)(3))
   4. The consequences of a subject’s decision to withdraw from the research and procedures for orderly closure of participation by the subject. (45 §46.116(b)(4))
   5. A statement that significant new findings developed during the course of the research, which may relate to subjects’ willingness to continue participation, will be provided to the subject. (45 §46.116(b)(1))
   6. The approximate number of subjects involved in the study. (45 §46.116(b)(1))
3. Where the potential for the need to report information to authorities exists (e.g., information arises in the course of the research that suggests a subject may intend to harm to him or herself or others, thus breaking confidentiality), subjects shall be informed before agreeing to participate in the study. (45 CFR §46.103(b))
4. The IRB may waive written documentation of informed consent if: (i) the research represents no more than minimal risk of harm to subjects, (ii) the waiver or alteration will not adversely affects the rights and welfare of the subject, (iii) the research could not be carried out without the waiver or alteration, and, (iv) where informed consent constitutes the only threat to anonymity, and (v) whenever appropriate, the subject ill be debriefed. When consent is waived, the IRB may require the investigator to offer subjects written information about the study. [45 CFR §46.116(c) and (d)]
5. Consent forms avoid jargon and should be written in the second person (e.g., If you agree to the research….) in a language and at a level that is understandable to the subject. 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. Informed consent will not be accomplished unless the requirement is met that the subject understands the components of the consent form.
6. Only the current IRB-approved watermarked version of the consent form may be used for consenting subjects.
7. The person who signs the consent form must be given a copy as a reference and reminder of the information conveyed by the researcher. Non-written methods of administering consent are also possible.
8. The ORSP will maintain an informed consent template on its web site. See Forms and Instructions and eIRB Home, Forms and Templates. PIs should follow the format of the consent template and its language whenever possible.
9. Please see the sections on Children in Research Involving Human Subjects, Internet Research and Cross-cultural research (including non-English speaking participants) for additional information on the informed consent process in these special research settings.

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Amendments (45 CFR §46.103(b)(4)

All amendments to currently approved research must be reviewed and approved by the IRB before implementation. Changes that do not increase the risk to research subjects may receive an expedited review. Modifications to approved research projects that are more than minimal risk and do not qualify for expedited review must be forwarded to the full IRB for review and, if appropriate, to those participating in the study by way of a revised informed consent.

The PI shall incorporate each approved revision to a research protocol or consent document into the approved protocol to ensure that there is only one complete protocol.

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Reviewing Reports of Adverse Events and Unanticipated Problems Involving Risks to subjects or Others (45 CFR §46.103(b)(5))

This section will help researchers distinguish between Adverse Events (AEs) and Unanticipated Problems (UPs), as well as guide PIs in determining when to report AEs and UPs to the IRB.

Unanticipated Problems

Events or problems that are unfavorable, harmful, or detrimental to the welfare of study subjects or other individuals involved with a research study AND that meet all of the following criteria are unanticipated problems (45 CFR 46.103(b)(5)):

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

Adverse Events

AE’s are not defined by Federal regulations. OHRP uses the term adverse event very broadly and includes any event meeting the following definition:

Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the participant’s participation in the research (modified from the definition of adverse events in the 1996 International
Conference on Harmonization E-6 Guidelines for Good Clinical Practice).

Adverse events encompass both physical and psychological harm. They occur most commonly in the context of biomedical research, although on occasion they can occur in the context of social and behavioral research. They may be caused by one or more of the following: a) the procedures involved in the research; b) an underlying disease, disorder, or condition of the subject; or c) other circumstances unrelated to the research or any underlying disease, disorder or condition of the subject.

What Needs to be Reported to the IRB

AEs that are NOT UPs do not need to be reported to the IRB. This means that the approved IRB protocol clearly specified the risks involved in the study and the adverse event was not unanticipated. Therefore, research participants were aware of the possibility of the AE occurring.

If, however, an AE occurs that was not anticipated, then the PI must report the AE to the IRB. The following questions may help determine whether the AE was unanticipated:

1. Is the AE unexpected? An unexpected AE is any AE that is not known or foreseeable as is described in the research protocol or other related sources of information, or is not consistent with the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the AE and the subject’s predisposing risk factor profile for the AE.
2. Is the AE related to or possibly related to participation in the research? Possibly related to means there is a reasonable possibility that the adverse event may have been caused by the procedures involved in the research.
3. Does the AE suggest that the research places the subjects or others at a greater risk for harm than was previously known or recognized? (NOTE: If an AE is serious then the answer is always “yes.”) To determine whether this criterion is met, first determine whether the AE is serious. That is, does it result in death, a life-threatening condition, hospitalization, disability/incapacity, congenital abnormality or birth defect, or medical intervention (surgery)? Also determine whether the research participants are placed at greater risk for experiencing physical or psychological concern than what was anticipated. If it is not serious, it still may require changes to the protocol.

All Unanticipated Problems must be promptly reported to the IRB and any other monitoring entity (e.g. department chair, sponsor). If the UP is serious then the PI must report it to the IRB within one (1) week of its occurrence. Any other UP should be reported to the IRB within two (2) weeks of its occurrence. All unanticipated problems should be reported to the HPA, the Interim Provost, the DHHS (if the research is federally-funded) and the sponsor (if applicable) within one month of the IRB’s receipt of the PI’s report of the problem.

Research investigators are responsible for reporting to both subjects and to the IRB significant findings developed in the course of the research that may relate to the subject's willingness to continue participation whether they qualify as UPs or AEs or not.

Examples

The case study below is an example of an unanticipated problem that must be reported under the DHHS regulations.

An investigator conducting behavioral research collects individually identifiable sensitive information about illicit drug use and other illegal behaviors by surveying college students. The data are stored on a laptop computer without encryption, and the laptop computer is stolen from the investigator’s car on the way home from work. This is an unanticipated (but not adverse event) problem that must be reported because the incident was (a) unexpected (i.e., the investigators did not anticipate the theft); (b) related to participation in the research; and (c) placed the subjects at a greater risk of psychological and social harm from the breach in confidentiality of the study data than was previously known or recognized.

An example of an adverse event that does not include unanticipated problems and does not need to be reported under 45 CFR §46 follows:

An investigator is conducting a psychology study evaluating the factors that affect reaction times in response to auditory stimuli. In order to perform the reaction time measurements, subjects are placed in a small, windowless soundproof booth and asked to wear headphones. The IRB-approved protocol and informed consent document describe claustrophobic reactions as one of the risks of the research. The twentieth subject enrolled in the research experiences significant claustrophobia, resulting in the subject withdrawing from the research. This example is not an unanticipated problem because the occurrence of the claustrophobic reactions – in terms of nature, severity, and frequency – was expected

The following is an example of an adverse event with an unanticipated problem that must be reported in the context of social and behavioral research because, although not serious, the adverse event was (a) unexpected; (b) related to participation in the research; and (c) suggested that the research places subjects at a greater risk of psychological harm than was previously known or recognized.

A behavioral researcher conducts a study in college students that involves completion of a detailed survey asking questions about early childhood experiences. The research was judged to involve no more than minimal risk and was approved by the IRB chairperson under an expedited review procedure.

During the completion of the survey, one student subject has a transient psychological reaction manifested by intense sadness and depressed mood that resolved without intervention after a few hours. The protocol and informed consent document for the research did not describe any risk of such negative psychological reactions. Upon further evaluation, the investigator determines that the subject’s negative psychological reaction resulted from certain survey questions that triggered repressed memories of physical abuse as a child. The investigator had not expected that such reactions would be triggered by the survey questions. In this example, the adverse event warranted consideration of substantive changes in the research protocol or informed consent process/document or other corrective actions in order to protect the safety, welfare or rights of subjects.

For studies submitted in eIRB, investigators shall report UPs and AEs by submitting a safety event. For paper studies, investigators shall submit a "Report of Adverse Event/Unanticipated Problems" found on the on the IRB website (Forms and Instructions).

The IRB chair and/or HPA and/or the convened IRB will review reports of any adverse events or unanticipated problems involving risks to subjects or others. Upon receipt of a report of an unexpected serious harm, the IRB will determine whether more detailed information is required, whether the study should be suspended or terminated and will report this to the Interim Provost for review. If necessary, the Interim Provost will report this to the Department of Health and Human Services (DHHS).

With the receipt of a report of an unexpected event that is not serious, the IRB may suggest a modification to the procedures to reduce the level of risk to subjects, or may require a modification to the consent form to include a description of the event. Any subsequent modification by the PI must be reviewed and approved by the IRB before implementation. Examples of corrective actions or substantive changes that might need to be considered in response to an unanticipated problem include:

1. changes to the research protocol initiated by the investigator prior to obtaining IRB approval to eliminate apparent immediate hazards to subjects
2. implementation of additional procedures for monitoring subjects
3. suspension of enrollment of new subjects
4. suspension of research procedures in currently enrolled subjects
5. modification of informed consent documents to include a description of newly recognized risks
6. provision of additional information about newly recognized risks to previously enrolled subjects
   

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Continuing Review (45 CFR §46.103(b)(4)

1. The IRB is required to re-evaluate research projects at intervals appropriate to the degree of risk but not less than once a year. For research involving no more than minimal risk, the approval period is generally one year from the date of the convened meeting at which the protocol was reviewed and approved. For research involving greater than minimal risk, the IRB will determine the appropriate approval period. Exempt research is subject to continuing review every three years.
   At the time of continuing review, the IRB must make the same determinations about risks, potential benefits, informed consent, and safeguards for human subjects, among other things, that were made at the time of initial review. The IRB must also determine whether any new information has emerged – either from the research itself or from other sources – that could alter the IRB’s previous determinations, particularly with respect to risk to subjects. Information regarding any unanticipated problems that have occurred since the previous IRB review in most cases will be pertinent to the IRB’s determination at the time of continuing review.
   
2. For applications originally processed in eIRB, investigators are required to submit a continuing review application via eIRB. For paper studies, a request for renewal is required for new or continuing analysis of identifiable information, new subject enrollment or follow-up meetings even after data collection is closed or continued data collection. Request for continuation is not required if enrollment and data collection are complete or was never begun or for continued analysis of a dataset that has been de-identified.
3. Continuing reviews may be either expedited or reviewed by the full board.
   a. Expedited review may occur where:
   1. the research is permanently closed to the enrollment of new participants, all participants have completed all research-related interventions, and the research remains active only for long- term follow-up of participants.
   2. no participants have been enrolled and no additional tasks have been identified.
   3. the remaining research activities are limited to data analysis. See also Expedited Review for more information.
      
      b. When the full Board reviews a request for continuing review, the approval date must occur within 1 year of the convened meeting at which: a) the protocol was approved without any conditions, b) the protocol was approved contingent on specific minor conditions that the IRB chair or his/her designee could verify; or c) the protocol with serious concerns or incomplete significant information that the IRB chair or his/her designee could verify is subsequently reviewed and approved at another convened meeting.
      The minutes of the IRB meetings shall document deliberations, actions and votes for each protocol undergoing continuing review by the convened IRB.
4. Review of currently approved or newly proposed consent/assent documents must occur during the scheduled continuing review of research by the IRB, but informed consent/assent documents should be reviewed whenever new information becomes available that would require modification of information in the informed consent/assent document.
5. There is no grace period extending the conduct of research beyond the expiration date of IRB approval. Therefore, the IRB and investigators must plan ahead to meet required continuing review dates. If the PI has failed to provide continuing review information to the IRB or the IRB has not reviewed and approved the protocol by the deadline, the research must stop, unless the IRB finds that it is in the best interests of individual participants to continue participating in the research interventions or interactions. Enrollment of new subjects cannot occur after the expiration of IRB approval.
6. If, after courtesy reminders sent 60 and 30 days prior to the expiration of an approval, no application for continuing review is received, the study will be administratively closed and the investigator, study team and IRB notified.

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Closure of Approved Research

If an investigator terminates the study, the investigator shall notify the IRB and shall:

1. Indicate the reason for closure (current activity status of the study)
2. Supply information on the subject numbers, complaints received, protocol deviations, variances or adverse events reported to the IRB
3. Supply any additional information the PI deems necessary to inform the IRB about the reasons for closure.

For paper studies, investigators submit a completed paper closure form. These forms are mailed to the investigator approximately 60 days prior to expiration of the approval and can be found on the IRB website, Forms and Instructions. For research applications originally processed in eIRB, automated notices are sent, 60 and 30 days before the expiration of the approval. The PI can request closure of the study at any time by completing a brief final report formin eIRB.

Once the PI has completed the research and so notified the ORSP, he or she may not recruit or enroll human research subjects. There can be no intervention, interaction or follow-up with enrolled human subjects, nor any continued collection of data or analysis of individually identifiable data previously collected as part of the research protocol.

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Noncompliance (45 CFR §46.103(b)(5)

The IRB shall be responsible for reviewing and determining all issues of serious or continuing noncompliance with 45 CFR §46 or IRB requirements. Any serious or continuing noncompliance shall be reported to the HPA and the IRB chair who together shall investigate all credible reports of alleged noncompliance and inappropriate involvement of human subjects in research.

Types of noncompliance (protocol deviations) include: Conducting research without IRB review, consent not obtained; wrong consent form used, failure to report serious adverse events or other problems, failure to maintain adequate records, failure to follow approved protocol, changing protocol without IRB approval, inadequate supervision, or inadequate training

Sources include: Reports of noncompliance may come from IRB members, investigators, subjects and their families, University personnel, anonymous sources, the media or the public.

1. Noncompliance issues may arise if the investigator fails to adhere to the IRB-approved protocol, to submit an amendment for review and approval before instituting the change(s), to report unanticipated problems involving risks to subjects, or to adhere to the ethical management and documentation required by the IRB.
2. When a report of alleged noncompliance is received by the HPA and/or IRB chair, a preliminary investigation will be undertaken and a determination will be made as to whether subjects are at risk or can be allowed to continue in the research while the investigation progresses. A preliminary administrative hold shall be put on the research if the IRB suspects or determines subjects are at risk.
3. The PI and advisor shall be required to meet with a subcommittee of the IRB (in such number to make a fair and justifiable decision) and the HPA to discuss the noncompliance issue and develop action plans to prevent recurrence and promote future compliance. The time and location shall be set by ORSP. Based on the severity of the noncompliance or the policies of the funding source, as applicable, the infraction may fall under the jurisdiction of the OHRP. Programs and findings and recommendations from this meeting shall be recorded and duly reported to the Interim Provost.
4. The IRB shall send a letter to the PI citing the alleged areas of noncompliance and the associated federal regulations and the corrective action plan. The PI will be asked to respond to the allegation and provide their specific plans to implement the proposed corrective action plan including a specified timeframe.
5. An audit may be conducted if the breadth of noncompliance of an ongoing study or study placed on administrative hold is not known. The audit may include only information requested from and provided by the PI or may require an onsite visit from an IRB subcommittee where original documentation is reviewed and/or observed. Any new areas of concern shall be reported in writing to the full IRB and placed on the IRB’s agenda for consideration in determining additional action (e.g., administrative hold of other studies under the purview of the PI, audit of other studies).
6. Actions the IRB may take:
   1. The IRB may determine that the research study is in compliance with Federal regulations and IRB policy and no further action is necessary.
   2. The IRB may decide that the PI found in noncompliance should not be allowed to process new protocols or renew current projects until all concerns have been addressed.
   3. The IRB may determine the research study under review is substantially in compliance with federal regulations and IRB policy but may make specific recommendations to improve or enhance the protections for the study’s human subjects or impose additional oversight such as:
      1. verifying subject selection is appropriate and observing the actual informed consent process,
      2. increasing monitoring of the research via data safety monitor or board and intervening as necessary through steps such as visits to the activity site and continuing evaluation to determine if any unanticipated risks to subjects or others have arisen,
      3. requesting a directed audit that target areas of concern,
      4. requesting a status report after subjects receive intervention,
      5. decreasing the continuing review cycle, or
      6. requesting additional PI/staff education focused on human subjects protection.
   4. The IRB may determine that the research study is not in compliance with federal regulations and/or IRB policy and/or that the PI’s response is not adequate to satisfy the committee’s concern. However, the IRB may conclude that the incident appears to be isolated and, in essence, a miscommunication or misunderstanding of a nonserious and noncontinuing nature. These cases should be promptly reported in writing to the IRB chair and the HPA. The IRB may impose restrictions and/or require additional subject protection such as:
      1. special reporting to and rigorous oversight by the IRB specific to the areas of concern (e.g., shortened continuing review intervals, follow-up audits or monitoring),
      2. oversight or mentoring by a department chair or more senior investigator,
      3. verifying that subject selection is appropriate and observing the actual informed consent process,
      4. monitoring the progress of the activity and intervening as necessary through such steps as site visits, continuing evaluation to determine if any unanticipated risks have arisen, and/or
      5. requesting an ad hoc review from an independent source with expertise in the type of research being conducted or expertise in the specific area of concern.
   5. The IRB may determine that the PI’s failures to comply with federal regulations and/or IRB policy pose such significant risks to subjects that the IRB may suspend or terminate its approval of the study for cause.
7. The investigator who believes the IRB has erred in its findings of noncompliance may submit a written request asking the IRB to reconsider. With the appeal and new information, the IRB may vote to confirm or modify its original findings and action.
8. The HPA shall facilitate and maintain documentation of all communication between the PI and the IRB. The HPA shall notify the IRB chair, Vice-Provost and department chair within 1 working day of any determination of noncompliance. The HPA shall maintain and update the IRB database or eIRB with current study information.
9. The Interim Provost shall make the final determination regarding scientific or faculty misconduct and any penalty/sanction that may be appropriate as well as whether or not any collected data may be used and under what conditions, according to institutional policies and procedures. The Interim shall notify the HPA. The HPA shall, in turn, notify the full IRB. The Interim Provost shall notify OHRP of any determinations of noncompliance.

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Suspension or Termination of IRB Approval of Research

1. The IRB has the 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 harm to subjects. (45 CFR §46.113)
2. Once a study has been terminated, human research subjects cannot be recruited or enrolled, there can be no intervention, interaction or follow-up with enrolled human subjects, nor any continued collection of data or analysis of data previously collected as part of the research protocol.
3. Any suspension or termination of approval by the HPA shall include a statement of the reasons for the action and shall be reported promptly to the investigator and advisor as well as to the IRB and Interim Provost.
4. The IRB has the authority to re-open terminated projects if it deems this action is necessary and in the best interests of the subjects.

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Appealing an IRB Decision

1. If the IRB makes a decision that an investigator believes to be unfair, unsubstantiated, or unduly restrictive on his or her proposed research, the investigator should first discuss the matter with the IRB chair and the HPA. The investigator should be prepared to present reasons that he or she believes that the proposed research is in compliance with University policy and Federal regulations for the protection of human subjects.
2. If the issue cannot be resolved satisfactorily by negotiation, the PI may appeal the decision, in writing, to the full IRB. The results of any negotiations that require approval by the full IRB will be taken to the next convened meeting for decision and vote.
3. In developing his or her appeal, the investigator is encouraged to seek the advice or opinion of an objective, qualified consultant to support the claim that the proposed research is in compliance with human subjects policy and regulations.
4. The investigator may appear before the IRB to present his or her appeal and any supportive material or documentation obtained through consultation, but the investigator cannot be present during the vote on the IRB’s final recommendation.

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Special Categories of Research and Sensitive Issues

Children in Research Involving Human Subjects

Definitions

• Assent: A child’s affirmative agreement to participate in research. Mere failure to object, absent affirmative agreement, should not be construed as assent.
• Children. Persons who have not attained the legal age for consent to treatment or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted. Residents under 18 years of age are considered children in North Carolina unless they are “emancipated” by court order or marriage or service in the military.
  • Emancipated minor: A legal status conferred upon persons who have not yet attained the age of legal competency as defined by state law, but who are entitled to treatment as if they had by virtue of assuming adult responsibilities, such as self-support, marriage or procreation.
  • Mature minor: Someone who has not yet reached adulthood (as defined by state law) but who may be treated as an adult for certain purposes (e.g., consent to medical care). A mature minor is not necessarily an emancipated minor.
• Guardian: An individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care.
• Parent: A child’s biological or adoptive parent.
• Permission: The agreement of parent(s) or guardian to the participation of their child or ward in research.

Categories of Research

The IRB can approve research involving children only if it falls into one of four categories, provided that all of the criteria for informed assent are also fulfilled. The IRB may exempt research involving children when the research involves only normal educational practices conducted in established or commonly accepted educational settings, the use of educational tests (cognitive, diagnostic, aptitude, achievement), or the observation of public behavior and the investigator does not participate in the activities being observed. The categories of research are as follows.

1. Research not involving greater than minimal risk to the children (45 CFR §46.404).
   Minimal risk for children involved in research should be the level of risk associated with the daily activities of a child. Risks include all harms, discomforts, indignities, embarrassments, and potential breaches of privacy and confidentiality associated with the research. Children experience different levels of risk; however, the fact that some children may be exposed daily to different levels of risks may not justify exposure to greater risks because of these circumstances. This category may meet the requirements for expedited level of review. Requires permission of one parent or guardian in the form of a signed informed consent document and assent of the child.
2. Research involving greater than minimal risk but with the prospect of direct benefit to the child (45 CFR §46.405). Requires permission of one parent or guardian in the form of a signed informed consent and that the IRB decides whether to require assent or not.
3. Research involving greater than minimal risk with no prospect of direct benefit to the child but likely to yield generalizable knowledge about the child’s disorder or condition (45 CFR §46.406). Requires permission of both parents or legal guardians in the form of a signed consent document and assent of the child. Exceptions to this requirement would include circumstances in which only one parent or legal guardian has legal responsibility for the care of the child.
4. Research that the IRB believes does not meet the conditions of 45 CFR §46.404, 405 or 406, but that presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children (45 CFR §46.407). Very rare.

Child Assent

When deciding whether children are capable of assent, the IRB considers:

• their age, maturity, and psychological state. Decisions may be made for all the children involved or on an individual basis.
• the form and content of the information conveyed to prospective children.
• that assent procedures reflect a reasonable effort to enable children to understand what participation would involve.

If adolescents are involved in research that would require a consent form if the subjects were adults, the IRB will require a similar written form to document assent.

• Written assent is required for those in high school (ages 15 to 17) and perhaps for those in middle school (ages 11 to 14).
• The one-page document must explain the purpose of the study, what will happen, risks involved, any benefits, the option to withdraw at any time, how confidentiality will be maintained, and contact information if the child has any questions.
• The assent form should include the following above the signature lines: “By printing/signing below, I agree to participate in the study.”

For children between the ages of 7 and 10, verbal assent may be obtained and documented by the PI. Depending on the child’s age and reading ability, a written document may be preferred to obtaining verbal assent.

If the project involves young children who cannot read (ages 6 and under), the PI may obtain verbal assent.

• The IRB requires a form that will document that assent took place. The form may consist of a brief (no more than one page), age-appropriate script of what the PI will say to the child (e.g., “We’re going to play some computer games. Do you want to play? You don’t have to if you don’t want to. You can stop playing anytime. If you have any questions about what you’re going to do, you can ask me, your teacher or your parents.”), and a checklist noting the child’s name, date of assent, and time of assent.
• If the child wants to stop participating at any time, he/she must be allowed to do so.

Judgments concerning assent may be made for all children to be involved in the research or may be made for each child, as the IRB deems appropriate. If the IRB determines that the capability of some or all of the children is so limited that they cannot reasonably be consulted, or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research, the assent of children is not necessary for proceeding with the research.

Even when the IRB determines that the subjects are capable of assent, the IRB may still waive the assent requirement under circumstances in which consent may be waived in accord with federal guidelines (see 45 CFR §46.116, subpart A) and the policy for waiver of informed consent laid out in this document. Federal regulations identify three circumstances when the IRB may waive assent:

• if the capability of some or all of the children is so limited that they cannot be consulted;
• if activities may directly benefit the children’s health or well-being and are available only in the research context;
• if the research meets the same conditions as those for waiver or alteration of informed consent with adults.

Assessing Understanding

The following questions can be used to assess whether the child understands what the study is about and what he or she is being asked to do as a subject.

• Tell me what this study is about.
• What do you think will happen to you in this study?
• What can you do if you don’t want to do something in the study?

Parental/Guardian Consent

Parental/guardian consent must be written in a language understandable to the parent or guardian and must include all the required elements of informed consent, e.g., the purpose of the research, the procedures during the study, length of the study, risks and benefits, alternative procedures available, how confidentiality will be maintained, compensation, and PI and ORSP contact information. The following statements must be included:

• Your child’s participation in this research is completely voluntary. Your child may refuse to participate even if you agree to his/her participation.
• Your child may discontinue participation at any time without penalty or loss of benefits.
• Your child may choose not to answer any question(s) for any reason.

In addition, for non-English speaking parents/guardians, the consent must be written in their primary language, with the translation attached; a short form written consent must be attached; and either the script (for young children) or written assent form must be presented.

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Cooperative and Cross-Campus Research (45 CFR §46.114)

Cooperative research projects are those projects covered by this policy which involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for safeguarding the rights of human subjects and complying with federal regulations.

1. Wake Forest University will ensure that any of its collaborating entities (i.e., those engaged in human subjects research by virtue of subject accrual, transfer of identifiable information, and/or in exchange of something of value, such as material support [e.g., money, drugs, or identifiable specimens], co-authorship, intellectual property, or credits) materially engaged in the conduct of non-federally sponsored research involving human subjects possesses mechanisms to protect human subjects that are at least equivalent to those procedures provided for in the ethical principles to which Wake Forest University is committed.
2. The University may enter into a joint review arrangement, rely upon the review of another qualified IRB with similar standards of human subjects protection, or be the reviewing IRB upon which another assured or non-assured institution relies. Such arrangements must be (a) in writing, (b) approved and signed by the IRB chair for proposed cooperative research between WFU and any other institution, and (c) approved and signed by correlative officials of the cooperating institutions. These arrangements may be entered into on a case-by-case basis, if arrangement is needed for the review of a single research project, or, for ongoing cooperative research, a more formal arrangement may be entered into, e.g., a memorandum of understanding detailing the joint review mechanism(s).
3. WFU and WFUHS are two legally separate entities and maintain separate FWAs. However, to accommodate the frequent collaboration among investigators from both campuses, the WFU IRB and WFUHS IRB have signed a Memorandum of Understanding concerning the reciprocal waiver of IRB oversight by the WFUHS and WFU IRBs for designated cooperative research. Under this agreement, each institution may rely upon the IRB review and continuing oversight of the other institution's IRB. Research involving medical testing, medical records and treatments is primarily conducted at WFUHS. Investigators select which IRB, WFU or WFUHS, will review the research with the eIRB application based on what the research entails and in some cases, where it is performed.
4. PIs involved in cooperative research must fully apprise the IRB of their research activities at any collaborating site(s). When the research activity involves an outside agency (e.g., hospital, public school, etc.), it is the responsibility of the investigator to determine if written approval from an appropriate official within the agency is required prior to conducting the research. Documentation that the agency does not require prior approval or the approval itself is included in the eIRB application.
5. Non-affiliated researchers seeking to recruit research subjects on the WFU campus must submit the approved protocol, informed consent (if applicable) and a copy of the study's approval letter from their institution's IRB. Electronic submission is preferred. If the HPA determines that the University is not engaged in the research, he/she shall forward the request to the appropriate University officials for their consideration. For example, if the project seeks to enroll graduate students, approval from the Dean of the Graduate School would be required.

Due to the overwhelming number of requests, the WFU Athletic Departments' policy does not allow recruitment of our student-athletes as research subjects for studies outside our University.

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Internet Research

The internet is being used increasingly in conducting human subjects research to collect, store and transmit data. Computer and internet-based research must address the same risks and levels of protection as other types of research involving human subjects. The researcher is encouraged to contact Information Systems for assistance in planning and execution of the research study, and to review the University’s computing policy posted at http://www.wfu.edu/technology/reference/policies/index.html.

Three Types of Research-Related Activities

1. Recruiting over the web. The IRB must review the text of the recruitment script to be presented to subjects and the context in which the recruitment takes place (e.g., posting a message on a newsgroup or creating a website to recruit subjects). The IRB must see an example of what the prospective subjects will see (i.e., a screen shot). All messages must show the PI’s name and affiliation with the University.
2. Observation of internet activity. Observation usually involves such activities as gathering information about the use of the internet and/or recording user information or users’ comments. Examples include (i) subject observation of an online discussion group using “cookies” to track web sites visited, or asking visitors to a web site to provide demographic information. The human subjects issues involved in this type of research generally involve consent/disclosure issues. Investigators must disclose their role as a researcher to group subjects. They also need to indicate to the IRB how they intend to obtain subjects’ consent to use this information for research.
3. Gathering Data. This type of research involves having subjects submit data (e.g., survey data) over the internet and presents the most serious human subjects concerns (e.g., obtaining consent, particularly assent from children) due to the potential limits to confidentiality.
   
   First, authentication (i.e., proper qualification and/or identification) of subjects is encouraged since failure to do so can threaten the integrity of research samples and the validity of research results. Researchers are encouraged to take such steps to authenticate subjects as providing subjects with a Personal Identification Number (PIN).
   
   Data transmitted via email cannot be anonymous without the use of additional steps such as data encryption that may require subjects to use a specific type or version of browser software. PI’s are caution that encryption standards vary from country to country and that there are legal restrictions on the export of certain encryption software outside the US. Almost all forms of email contain the sender’s email address. In order to maintain anonymity, the research must use an “anonymizer” – a third party site that strips off the sender’s email address. Technical procedures (e.g., firewalls, encryption, password security) must be included in the protocol narrative.

Online surveys should be designed to allow the subject to skip questions. It must explain the options that are available, if any, for retrieving and discarding responses and must allow "no response" as an option for every question.

Server Administration

Data submitted over the Web can only be anonymous if software is used to store the information directly in a database without identifiers; otherwise identifiers are attached to the data. Web servers automatically store a great deal of personal information. If the PI chooses to run a separate server for data collection and/or storage, the server must be set up under the guidance of WFU's Information Systems or the department’s ITG. The IRB recommends that access to the server be limited to key project personnel.

Data Storage/Disposal

If a server is used for data storage, personal identifying information should be kept separate from the data and should be stored in encrypted format. Data backups should be stored in a secure data room environmentally controlled and with limited access. Complete data destruction services should be used to ensure no data can be recovered from obsolete electronic media. Storing electronic data on the ThinkPad is not necessarily a secure method. Storing data on shared files may also be risky. Data backups should be stored in a secure data room environmentally controlled and with limited access. When data are no longer needed, complete data destruction services should be used to ensure that no data can be recovered from obsolete electronic media.

Risks

Research on the internet presents new concerns to human subjects issues: risk, consent, participation by children, and confidentiality. PIs must provide technical information on how they address these issues.

Two sources of potential harm from internet research are:

• harm resulting from participation in the research (e.g., acute emotional reactions to certain questions). Since there is generally no direct contact with subjects in research over the internet, it may be difficult or impossible to deal with individual subject reactions. Consequently, sensitive research may not be appropriate for the internet.
• harm resulting from breach of confidentiality. PIs need to address how they intend to ensure confidentiality. The degree of concern over confidentiality will be directly related to the sensitivity of the data.

Informed Consent

When anyone who can access the internet is a potential subject, it is important to ensure potential subjects read and understand the consent information. Ensuring comprehension may be accomplished by: a) incorporating short questionnaires within the consent process to assess the potential subject’s understanding of the information presented online, or b) asking subjects to contact the researcher to discuss the information presented before beginning participation.

Innocuous research on non-sensitive topics conducted over the internet may not need documentation of consent. When a signed consent form is not required, PIs can use a “portal”; i.e., where subjects must click on a consent page to get to the rest of the research. Requesting a waiver of consent is often appropriate for low risk research conducted on the internet.

Where signature is required, PIs can have subjects submit a signed consent form and send them a password to gain access to the research pages or b) announce the study, provide the watermarked IRB-approved consent form in pdf format and have the subjects download and mail the form to the PI. At that time the PI could give the subject the password to access the study. In any case, PIs must indicate how they plan to obtain consent from subjects or request a waiver of this requirement.

The process for obtaining online consent usually includes a written statement of the basic elements of the consent on a watermarked document that includes a statement such as, “Clicking below indicates that I have read and understood the description of the study and I agree to participate.” The subject can then print a hard copy for his/her records and return a second signed copy to the researcher if so requested.

Participation by children. The IRB has the authority to waive the requirement for parental permission; when the research qualifies for such a waiver no additional safeguards for children are required.

• Either children can participate without permission or subjects can attest in a simple consent statement that they are over 18 years of age.
• Where parental permission is required, PIs can use passwords as above.
• To screen out children completely from the research (although no system can guarantee that children are not participating), PIs can use Internet Monitoring Software (SafeSurf and RSAQ ratings) or use Adult Check systems.

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Cross-Cultural Research

Research conducted in different cultural contexts can take place within and outside the United States. The former would consist of research with subjects from cultural minorities in the United States, the latter with subjects living in different nations.

Local Research Context

Respect for the culture and context of the research environment is an important criterion in assessing the procedures followed in the research. Investigators must understand the context of the locality in which they are conducting research in order to protect the rights and welfare of the subjects. Cultural knowledge includes knowledge about socioeconomic, political, and cultural factors that influence every part of the research domain. For example, questions may be meaningful in a mainstream European American context, but lose their meaning or are offensive in other cultural contexts. Furthermore, cultures have different authority structures that will influence how researchers handle potential coercion and this, too, must be considered.

Research Team

• The investigators themselves must demonstrate cultural knowledge and sensitivity in the research application, the informed consent, and the protocol document.
• If researchers do not have direct knowledge of the local research context, the IRB recommends investigators collaborate with researchers knowledgeable about the culture of the research subjects. If qualified researchers are not available, the researcher should seek informants for the research team whose cultural backgrounds are the same as the respondents.
• The researcher will want to consider having research assistants with the same cultural background as the subjects conduct the research to improve the chances of respectful and culturally appropriate treatment of the subjects. These research assistants, however, should not be too close to the subjects, because in many cultures subjects would not be free to refuse to cooperation with the researcher if a known other asks them to participate.

Research in the United States

Research involving cultural minorities in the United States must conform to 45 CFR §46, as outlined in this document. The researcher should be aware that, even if these minorities speak English, they may be more comfortable speaking and reading forms in their native language. Their customs and cultural norms may be different and may include sensitivities toward or mistrust of mainstream western investigators or institutions. In these cases, proper conduct is not just the absence of discrimination, but it implies actively seeking to understand the social position and sensitivities of members of the minority group and preparing consent materials (oral or written) in the language they are most comfortable using. Collaboration with representatives of the minority group is advisable, both to gain insight into the subjects’ attitudes and expectations and to ensure smooth communication during the research.

The investigator must demonstrate cultural sensitivity to the IRB. His/her eIRB application and protocol document must describe how the research will address the issues raised when research involves non-English speaking subjects. See also informed consent for non-English speaking subjects.

Research Conducted in Other Countries

Research is either conducted with or without foreign collaborators. If it is done with foreign collaborators, the foreign research institution is either engaged or not engaged.

1. A foreign institution is engaged when it recruits subjects and secures consent from the subjects or when it conducts research procedures, or receives or shares private, identifiable information (e.g., a university in Tokyo that conducts an experiment with human subjects paid for by a US investigator supported by NIH).
2. An institution is not engaged if the extent of its involvement is to provide access to the potential subjects, provide information to the potential subjects, or give research personal information about subjects for which written permission has already been secured.
   
   The protection of the rights and welfare of subjects in foreign countries follows one of three procedures, depending on the role of foreign research collaborators:
   1. Research Without Foreign Collaborators. Some international research is done without the involvement of collaborators (e.g., a political scientist interviewing people on the street in Germany). This type of research has to be submitted to Wake Forest University’s IRB, following the procedures outlined in this document. Although federal regulations do not require review at a foreign research site, local review of some sort may be the norm in some countries. The researcher must be able to demonstrate his/her expertise on local norms to the IRB.
   2. Research With an Engaged Institution in a Foreign Country. When an engaged foreign institution has rules in place that ensure a subject will be protected in a manner that is equivalent, but not necessarily similar to those outlined in Wake Forest University’s IRB policy, the foreign country’s procedures may be substituted for the procedures required by US Federal regulations and WFU’s policies. Written descriptions of the specific policies that have been adopted by a foreign institution should be provided to the IRB if these policies deviate significantly from the policies and procedures contained herein.
   3. Research With a Non-engaged Institution in a Foreign Country. If the collaborating institution is not ‘engaged’ foreign assurances of compliance are not required.

Some internet research may be considered international research. See also Internet Research.

Obtaining and Documenting Informed Consent for Non-English Speaking Subjects (See also Cross-Cultural Research.)

1. Informed consent document should be in a language understandable to the subject. (45 CFR §46.116)
2. There are two procedures for obtaining consent from non-English speakers, of which the first is preferable whenever possible:
   1. When the study proposes to enroll non-English speaking subjects:
      • an informed consent form should be prepared that meets all the requirements.
      • If the original informed consent form was written in English, a translation should be prepared and submitted to the IRB, together with the English original. The researcher should indicate in the study narrative how quality of the translation has been assured (e.g., investigator's fluency in the language, translation and back translation into English; a certified translator) and explain any changes in language that were necessary to make the informed consent form appropriate for the non-English speaking context.
      • If the original informed consent form was written in the language of the non-English speaking subjects, it should be submitted to the IRB, together with a translation in English.
        
        
   2. If a non-English speaking subject is unexpectedly screened and investigators do not have a written translation of the consent document, the investigator can either exclude the subject, or rely on an oral translation of the informed consent form by a translator who is fluent in both the language of the subject and English.
      
      The translator should orally present to the subject the text of the English informed consent form, as approved by the IRB. In doing so, the translator should be sure to include at least the information listed by the “short form” written consent document. When this procedure is used, the English version of the informed consent document should be signed by the translator and a foreign language version of the short form should be signed by the subject and the translator. A copy of the short form and summary must be given to the subject or his/her representative. Note: If no translator is available, investigators should carefully consider the ethical and legal ramifications of enrolling the subjects in the study when language barriers exist. If the subject does not clearly understand the information presented, the subject’s consent will not be truly informed and may not be legally effective.
3. When research involves very low levels of risk to subjects and the subjects are illiterate, it is sufficient to read aloud the informed consent document and summary and obtain consent verbally. A witness other than the researcher should sign a document attesting to the verbal consent under these circumstances. When signing an informed consent document itself presents a risk, as in the case of illegal immigrants to the United States, a similar procedure may be followed.

Research Outside the United States

1. All informed consent procedures must take place in the local language of the subjects. If the original informed consent form was written in English, a translation into the local language should be prepared and submitted to the IRB, together with the English original. The researcher should indicate in the protocol document and the eIRB application how quality of the translation has been assured (e.g., fluency of the PI, translation and back translation into English; a certified translator) and explain any changes in language that were necessary to make the informed consent form appropriate for the foreign context.
   
   If the original informed consent form was written in the language of the local subjects, it should be submitted to the IRB, together with a translation in English. The contact information of local personnel rather than Wake Forest personnel should be listed on the consent form for research outside the United States.
   
   
2. When a written informed consent form poses difficulties because written evidence of participation in research either endangers the subjects’ position or is in violation with cultural norms, ideas and expectations, the researcher may obtain informed consent orally, if so approved by the IRB. A witness other than the researcher should sign a document attesting to the verbal consent under these circumstances. The researcher should justify and explain to the IRB why a written consent would be culturally inappropriate.

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Incomplete Disclosure and Deception in Research

1. Research involving deception will not be approved unless the IRB has determined that the use of deceptive techniques is justified by the study’s significant scientific, educational, or applied value and that effective nondeceptive alternative procedures are not feasible.
2. Researchers must not deceive prospective subjects about research that is reasonably expected to cause physical pain or severe emotional distress.
3. Investigators must explain any deception that was an integral feature of the design and conduct of an experiment to subjects as early as is feasible, preferably at the conclusion of their participation, but no later than at the conclusion of the data collection, and permit subjects to withdraw their data. Under conditions in which data are anonymous, the requirement to allow data withdrawal is not practical, the subject should be reminded about the anonymity of the data and invited to discuss any concerns with the PI.
4. PIs must provide a prompt opportunity for subjects to obtain appropriate information about the nature, results, and conclusions of the research, and they must take reasonable steps to correct any misconceptions that subjects may have of which the investigators are aware.
5. If scientific or humane values justify delaying or withholding this information, researchers must take reasonable measures to reduce the risk of harm.
6. If and when an investigator becomes aware that research procedures have harmed a subject, they must take reasonable steps to minimize and repair the harm.
7. Confederates enlisted as part of an approved deception are considered study team members and therefore must have completed CITI certification and be listed on the application before the research is approved.

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Privacy Protection

Under circumstances in which there is concern that disclosure of identifying information could be compelled, researchers should apply for a Certificate of Confidentiality. The ORSP can help with this application process. Examples of research that can be considered sensitive include:

1. Information relating to sexual attitudes, preferences, or practices.
2. Information relating to the use of alcohol, drugs, or other addictive products.
3. Information pertaining to illegal conduct.
4. Information that if released could reasonably be damaging to an individual’s financial standing, employability, or reputation.
5. Information that would normally be recorded in a patient's medical record, and the disclosure of which could reasonably lead to social stigmatization or discrimination.
6. Information obtaining to an individual’s psychological well-being or mental health.
7. Genetic information.

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Research Involving Sensitive Issues

1. Research questions that focus on sensitive issues may cause considerable mental discomfort for some of the subjects.
   
   Mental discomfort during or after the research may be prompted by research in which subjects are asked to recall and report on current or past feelings and behaviors that are unpleasant, harmful or risky, potentially threatening to self-image or self-ideals, potentially stigmatizing or socially disapproved.
2. Researchers conducting research involving sensitive issues must mention the potential for discomfort in the informed consent.
3. Researchers conducting studies involving sensitive issues must make subjects aware of the availability of counseling after participation in the experiment, if this participation caused them to feel considerable mental discomfort.
   
   The potential need for counseling can be described either in the IRB-approved informed consent document or in an IRB-approved debriefing script.
   An example of some sample text could be:
   “During this research study, you were asked about some potentially sensitive issues (e.g., sexual orientation and sexual practices). We understand that discussing these issues may have caused you to feel uncomfortable. If you experience discomfort (sadness, anger, etc.), we advise you to talk with one of the professionals at [the following service]."
   1. For Reynolda campus students participating in research, we recommend referral to the University Counseling Center at Wake Forest University (758-5273).
   2. For students from the Bowman Gray campus participating in research on the Reynolda campus, we recommend referral to the Psychiatry department 336/716-4551 for adult consults and 336/716-9606 for children and adolescent consults.
   3. To select an appropriate service for referral of other research subjects, contact FIRST Line at 336/703-3000, http://www.forsyth.cc/Library/first_line.aspx. FIRST Line, a service of the Forsyth County library:
      1. Provides comprehensive generic human service information about and referral to human service agencies available to residents of Forsyth County.
      2. Assists other agency professionals in making appropriate referrals for their clients.
      3. Maintains an extensive database of support groups, civic organizations, clubs, special interest groups, and current local events.

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Helpful Information

Contacts include the following:

Interim Provost, Dr. Mark Welker, PO Box 7486; 336/758-3898 (5758), fax 336/758-3853(4321); welker@wfu.edu

2011-2012 IRB Chair, Dr. Janine Jennings, Psychology Department, 336/758-3632; jenningj@wfu.edu.

2011-2012 IRB Vice-Chair, Dr. Steven Giles, Communication Department, 336/758-4442; gilessm@wfu.edu

Office of Research and Sponsored Programs, Wake Forest University – Reynolda Campus, 306 Reynolda Hall, PO Box 7528; 336/758-5888, fax 336/758-1959.
Lori Messer, Director, 336/758-5888; messerlj@wfu.edu
Pam Moser, Associate Director for Faculty Research Compliance and Support and Human Protections Administrator (HPA), 336/758-5195; moserpc@ wfu.edu.

For more information on the IRB, please visit the IRB website (www.wfu.edu/rsp/irb/). You may also call the Office of Research and Sponsored Programs at 336/758-5888.

The following websites offer useful information for the human subjects researcher:

Belmont Report (Ethical Principles and Guidelines)
hhs.gov/ohrp/humansubjects/guidance/Belmont.htm

Declaration of Helsinki
www.wma.net/e/ethicsunit/helsinki.htm

Nuremberg Code
www.aches-mc.org/nurm.htm

OHRP (Office for Human Research Protection under DHHS; formerly OPRR [Office for Protection for Research Risks])
hhs.gov/ohrp

IRB Forum. www.mcwirb.org

ARENA (Applied Research Ethics National Association)
www.primr.org/arena.html

Informed Consent Tutorial from the University of Minnesota
http://www.research.umn.edu/consent/menu_soc.html