Wake Forest University--Reynolda Campus
Institutional Review Board Policies and Procedures
Statement of Ethical
Principles of Research
Definitions and Applicability
Codes of Conduct
Establishment of an Institutional Review Board
Authorized Institutional Official
Human Protections Administrator
The Institutional Review Board
Institutional Review Board and the Review Process
The IRB and the Review Process
Levels of Review
Procedures for IRB Review
Informed Consent Process
Events and Unanticipated Problems
Closure of Approved Research
or Termination of IRB Approval
Appealing an IRB Decision
Categories of Research and Sensitive Issues
in Research Involving Human Subjects
Cooperative and Cross-Campus
Incomplete Disclosure and Deception in Research
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Wake Forest University – Reynolda Campus
Institutional Review Board Policies and Procedures
Ethical Principles of Research
- The three basic ethical principles for the conduct of human
subjects research, as set forth in The Belmont Report (Ethical
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
- Respect for Persons. Individuals participating
in research shall be treated as autonomous human beings.
Extra protection shall be provided to those with limited
- 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.
- 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.
- 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.
- 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
- 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 that is without a favorable risk-benefit ratio will
- 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)
- The Reynolda Campus of Wake Forest University has adopted the
Research means a systematic investigation (including research
development, testing and evaluation) designed to contribute to generalizable
Human subject means a living individual about whom
an investigator (whether
faculty or student) conducting research obtains:
IRB means an Institutional Review Board established in
accord with and for the purposes expressed in this policy.
- data through intervention or interaction with the individual,
- 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
- Private information must be individually identifiable
if obtaining the information is to constitute research involving
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
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
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.
- 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:
- the research is sponsored by this institution; or
- 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
- 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;
- 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
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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
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
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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,
termination of the FWA. Both the FWA and registration of the University’s
required under the OHRP Federalwide Assurance, are maintained in the
Research and Sponsored Programs.
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Establishment of an Institutional Review Board
- 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.
- 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
- 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))
- 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))
- The University will provide training and educational opportunities
for the IRB, investigators, professional and support staff supporting
- 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
- The University has the responsibility to provide adequate resources
to allow the IRB to meet its Federal and University mandates.
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- Authorized Institutional Official. Safeguarding the
rights and welfare of human subjects in research is a general
institutional policy delegated by the President through the Associate Provost for Research. 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))
- 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:
- 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
- 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))
- Meeting agendas. Prepare an agenda and distribute
it at least one weeks prior to the IRB meeting.
- 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))
- Maintain a current list of IRB members with credentials,
department affiliation and relationship to WFU. (45 CFR §46.103(b)(3))
- 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
- Monitor mandatory human subjects education certification/recertification
of IRB members, PIs and other personnel as required.
- 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.
- 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.
- Maintain a web site which includes information about the
IRB, its membership, meeting dates, instructions
and forms, and policies and procedures.
- 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)
- Keep the IRB informed of the status of all research protocols. (45 CFR
- 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
- 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:
- complex projects involving unusual levels or types
of risk to subjects,
- projects conducted by investigators who previously
have failed to comply with federal regulations or IRB
- 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 Associate Provost for Research and will make recommendations concerning actions to be taken
in light of any material violations of protocol.
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The Institutional Review
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
- 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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Wake Forest University (WFU) has established its IRB membership
requirements in accordance with the compositional requirements of
45 CFR §46.107.
The Associate Provost for Research 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.
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
- Invitation. After consultation with appropriate department
chairs, invitation to membership on the IRB shall be extended in
writing by the Associate Provost for Research.
- Composition (45 CFR §46.107)
- 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.
- 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))
- 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)
- 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))
- 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))
- 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.
- 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.
- Responsibilities of IRB Members
- IRB members:
- shall be appointed to the IRB by the Associate Provost for Research 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 Associate Provost for Research and may be reappointed at the conclusion of
their term. Removal by the Associate Provost for Research 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
- 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
- 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))
- 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 Associate Provost for Research 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
- 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.
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IRB Meetings (45 CFR §46.108(b))
- 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.
- Convened meetings
- 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.
- 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 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.
- 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
- All investigators and key personnel involved
in research with human subjects must complete
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
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.
- Those key personnel who have completed training elsewhere may submit documentation of completion to the HPA. The Associate Provost for Research determines whether or not the training satisfies the requirements of Wake Forest University.
- The IRB may require that additional project personnel receive
educational training as a prerequisite for project approval if
deems this necessary to ensure the welfare of the subjects.
- IRB members
and ORSP staff supporting the IRB are required
CITI training and OHRP’s
- The Associate Provost for Research may make changes in these
education and training requirements, as appropriate. PIs should
contact the HPA or the Associate Provost for Research to obtain
updated and complete information about requirements for mandatory
Recertification and Ongoing Education
- 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.
- 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 Associate Provost for Research shall
make decisions concerning the content requirements for certification
- 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:
- Research proposals reviewed, approved consent and assent documents, amendment requests, continuing review applications, safety events and other research-related documents as needed.
- 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.
- Records of continuing review activities.
- Correspondence between the IRB and the investigators.
- A list of IRB members in the same detail as described in 45 CFR
- Written procedures for the IRB in the same detail as described
in 45 CFR §46.103(b)(4) and (5).
- 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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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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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)
- The IRB chair or designee shall determine whether a given activity
can be considered human subjects research.
- 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
- 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.
- Respect for Persons
- Where appropriate, the IRB shall require adequate provisions
to protect the privacy of subjects and to maintain the
confidentiality of data.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Where appropriate, research plans shall make adequate
provision for monitoring the data collected to ensure the
safety of subjects.
- Risks to subjects shall be minimized:
- by using procedures that are consistent with sound
research design and do not unnecessarily expose subjects
to risks, and
- whenever appropriate by using procedures already
being performed on the subjects for diagnostic or
- 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.
- Selection of subjects shall be equitable. When appropriate,
every effort will be made to include subjects of diverse
age, race, gender, and ethnicity.
- 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.
- 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.
- The investigator should ensure that consent for participation
is sought only under circumstances that minimize the possibility
of coercion or undue influence.
- 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
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
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.
- When employees are involved in research, the researcher
must be able to provide justification other than convenience
for their involvement.
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- 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))
- The IRB shall adopt appropriate procedures to implement these
policies with the advice and counsel of the ORSP.
- 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))
- 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
- 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.
- The IRB shall require documentation of informed consent or may
waive documentation in accordance with 45 CFR §46.117.
- 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.
- 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.
- 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
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 is not subject to IRB federal regulations and does not require
- 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
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.
- 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
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Research involving materials (data, documents, records or
specimens) that have been collected, or will be collected solely
for non-research purposes.
- Collection of data from voice, video, digital, or image recordings
made for research purposes.
- 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.
- 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).
- 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.
- The IRB may use the expedited review procedures to review minor
changes in previously approved research during the period for which
approval is authorized.
- Expedited review is carried
out by an IRB member.
- 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.
- 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.
- 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
- The IRB may require full review of any research
submitted or approved under expedited review and any research not
approved by expedited review.
- 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.
- Examples of research activities that must be reviewed by the
full IRB include:
- 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.
- 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”.
- Non-curricular, interactive research in primary and secondary
- 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.
- Some research involving special populations, e.g., children, pregnant women and mentally incompetent persons.
- 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
- 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.
- 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.
- Before a research application can be approved, it must receive
the approval of the majority of those voting members present at
the convened meeting.
- The IRB will make one of four determinations regarding an application:
- Forward for approval without questions, concerns or requests
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- Criteria for IRB approval of research include the following:
- Risks to subjects are minimized by using procedures that
are consistent with sound research design and do not unnecessarily
expose subjects to risk.
- 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
- Selection of subjects should be conducted in an equitable
manner and recruitment procedures should be free of coercion.
- The proposed research considers the privacy rights of
subjects and protects
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.
- 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
- 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
- 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))
- 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.
- 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.
- The basic elements of the informed consent (45 §46.116)
- A statement that the study involves research. (45 §46.116(a)(1))
- An explanation of the purpose of the research. (45 §46.116(a)(1))
- The expected duration of the participation. (45 §46.116(a)(1))
- 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))
- A description of any reasonably foreseeable risks or discomforts
to the subject. (45 §46.116(a)(2))
- 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.
- 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.
- 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))
- 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))
- 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
- 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))
- Additional requirements may include:
- 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))
- Anticipated circumstances under which participation may be
terminated by the investigator without regard to the subject’s
consent. (45 §46.116(b)(2))
- Any additional costs to the subject that may result from
participation in the research. (45 §46.116(b)(3))
- 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))
- 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))
- The approximate number of subjects
involved in the study. (45 §46.116(b)(1))
- 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))
- The IRB may waive written documentation of informed consent
if: (i) the research represents no more than minimal risk of harm
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,
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
- 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
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.
- Only the current IRB-approved watermarked version of the consent form may be used for consenting subjects.
- 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.
- 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
- 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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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.
Events or problems that are unfavorable, harmful,
or detrimental to the welfare of study subjects or other individuals
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
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
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,
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:
- 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.
- 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.
- 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 Associate Provost for Research, 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
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.
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
information about illicit drug use and other illegal behaviors by surveying
students. The data are stored on a laptop computer without encryption, and
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
research did not describe any risk of such negative psychological reactions.
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 Associate Provost for Research
for review. If necessary, the Associate Provost for Research 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:
- changes to the research protocol initiated by the investigator
prior to obtaining IRB approval to eliminate apparent immediate
hazards to subjects
- implementation of additional procedures for monitoring subjects
- suspension of enrollment of new subjects
- suspension of research procedures in currently enrolled subjects
- modification of informed consent documents to include a description
of newly recognized risks
- provision of additional information about newly recognized
risks to previously enrolled subjects
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Continuing Review (45 CFR §46.103(b)(4)
- 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,
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.
- 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.
- Continuing reviews may be either expedited or reviewed by
the full board.
a. Expedited review may occur where:
- 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.
- no participants
have been enrolled
and no additional tasks have been identified.
- the remaining research
activities are limited to data analysis. See also Expedited Review for more
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
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.
- Review of currently approved or newly proposed consent/assent
documents must occur during the scheduled continuing review
of research by the IRB,
consent/assent documents should be reviewed whenever new information
becomes available that would require modification of information
in the informed
- There is no grace period extending the conduct of research
beyond the expiration date of IRB approval. Therefore, the
IRB and investigators
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
after the expiration of IRB approval.
- 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:
- Indicate the reason for closure (current activity status of the
- Supply information on the subject numbers, complaints received,
protocol deviations, variances or adverse events reported to the
- 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
to report serious adverse events or other problems, failure to maintain
adequate records, failure to follow approved protocol, changing
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.
- 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.
- 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.
- 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 Associate Provost for Research.
- 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.
- 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).
- Actions the IRB may take:
- The IRB may determine that the research study is in compliance
with Federal regulations and IRB policy and no further action
- 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.
- 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:
- verifying subject selection is appropriate and observing
the actual informed consent process,
- 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,
- requesting a directed audit that target areas of concern,
- requesting a status report after subjects receive
- decreasing the continuing review cycle, or
- requesting additional PI/staff education focused on human
- 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:
- 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),
- oversight or mentoring by a department chair or more senior
- verifying that subject selection is appropriate and
observing the actual informed consent process,
- 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
- 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.
- 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.
- 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.
- The HPA shall facilitate
and maintain documentation of all communication between the PI
the IRB. The HPA shall notify the IRB chair, Vice-Provost and department chair within 1 working day
any determination of noncompliance. The HPA shall maintain
and update the IRB database or eIRB with current
- The Associate Provost for Research 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 Associate Provost for Research
shall notify OHRP of any determinations of noncompliance.
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or Termination of IRB Approval of Research
- 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)
- 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.
- 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
Associate Provost for Research.
- The IRB has the authority to re-open terminated projects if it
deems this action is necessary and in the best interests of the
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Appealing an IRB Decision
- 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.
- 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.
- 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.
- 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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Categories of Research and Sensitive Issues
in Research Involving Human Subjects
- 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
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
- 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
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
and the investigator does not participate in the activities being
observed. The categories of research are as follows.
- 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
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
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.
- 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.
- Research involving greater than minimal risk with no prospect of
direct benefit to the child but likely to yield generalizable
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.
- 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
§46.407). Very rare.
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
- 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
- The one-page document must explain the purpose of the study,
what will happen, risks involved, any benefits, the option
withdraw at any time, how confidentiality will be maintained,
and contact information if the child has any questions.
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
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.
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
- 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
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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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
- 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.
- 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
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).
- WFU and WFUHS are two legally separate entities and
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.
- 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.
- 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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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
- 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.
- 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.
- 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
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
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.
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
a separate server for data collection and/or storage, the server
must be set up under the guidance of WFU's Information Systems or
ITG. The IRB recommends that access to the server be limited
to key project personnel.
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.
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
be recovered from obsolete electronic media.
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.
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
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
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
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
- 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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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.
- 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
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.
- 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).
- 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
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:
- Research Without Foreign Collaborators. Some international
research is done without the involvement of collaborators
a political scientist interviewing people on the street in
Germany). This type of research has to be submitted to Wake
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.
- 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
should be provided to the IRB if these policies deviate significantly
from the policies and procedures contained herein.
- Research With a Non-engaged Institution in a Foreign
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.)
Discussions with non-English speakers about their participation
in a study should always be conducted with a translator who is fluent
in both English and the language of the subject. The translator
may be a member of the study team, but should not be a family member
or intimate of the subject.
- Informed consent document should
be in a language understandable to the subject. (45 CFR §46.116)
- There are two procedures for obtaining consent from non-English
speakers, of which the first is preferable whenever possible:
- 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
translation has been assured (e.g., investigator's fluency
in the language, translation and back translation into
English; a certified translator)
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
- If a non-English speaking subject is unexpectedly screened
and investigators do not have a written translation of the
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
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
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
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
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.
- 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
- 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.
- 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
- 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.
- Researchers must not deceive prospective subjects about research
that is reasonably expected to cause physical pain or severe emotional
- 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.
- 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
- If scientific or humane values justify delaying or withholding
this information, researchers must take reasonable measures to reduce
the risk of harm.
- 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.
- 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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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
- Information relating to sexual attitudes, preferences, or practices.
- Information relating to the use of alcohol, drugs, or other addictive
- Information pertaining to illegal conduct.
- Information that if released could reasonably be damaging to
an individual’s financial standing, employability, or reputation.
- 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.
- Information obtaining to an individual’s psychological
well-being or mental health.
- Genetic information.
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- 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.
- Researchers conducting research involving sensitive issues must
mention the potential for discomfort in the informed consent.
- 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]."
- For Reynolda campus students participating in research, we
recommend referral to the University Counseling Center at Wake
Forest University (758-5273).
- 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.
- To select an appropriate service for referral of other research
subjects, contact FIRST Line at 336/703-3000,
FIRST Line, a service of the Forsyth County library:
- Provides comprehensive generic human service information
about and referral to human service agencies available to
residents of Forsyth County.
- Assists other agency professionals in making appropriate
referrals for their clients.
- Maintains an extensive database of support groups, civic
organizations, clubs, special interest groups, and current
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Contacts include the following:
Associate Provost for Research, Dr. S. Bruce King, PO Box 7486; 336/758-5774, fax 336/758-4656; email@example.com
2012-2013 IRB Chair, Dr. Janine Jennings, Psychology Department, 336/758-3632; firstname.lastname@example.org.
2012-2013 IRB Vice-Chair, Dr. Fred Chen, Economics Department, 336/758-5231; email@example.com
Office of Research and Sponsored Programs, Wake Forest University – Reynolda
Campus, 306 Reynolda Hall, PO Box 7528; 336/758-5888.
Pam Moser, Associate Director for Faculty Research Compliance and Support and Human Protections Administrator (HPA), 336/758-5195; moserpc@ wfu.edu.
Amy Comer, Associate Director, 336/758-4228; firstname.lastname@example.org.
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
Belmont Report (Ethical Principles and Guidelines)
Declaration of Helsinki
OHRP (Office for Human Research Protection under DHHS; formerly OPRR
[Office for Protection for Research Risks])
IRB Forum. www.mcwirb.org
ARENA (Applied Research Ethics National Association)
Informed Consent Tutorial from the University of Minnesota