NOTE: THIS GUIDANCE HAS
BEEN REPLACED BY OHRPíS JANUARY 15, 2007 GUIDANCE ON WRITTEN IRB
PROCEDURES. CLICK HERE FOR THE JANUARY 15, 2007 GUIDANCE. THIS
GUIDANCE HAD REPLACED OHRPíS APRIL 2,
2002 GUIDANCE ENTITLED, "OHRP GUIDANCE ON WRITTEN IRB PROCEDURES." CLICK
HERE FOR THE
APRIL 2, 2002 GUIDANCE.
Office for Human Research Protections
Department of Health and Human Services
Guidance on Written IRB Procedures
Date: July 11, 2002
Scope: This document outlines the required elements of
written Institutional Review Board (IRB) procedures under Department of
Health and Human Services (HHS) regulations for the protection of human
subjects (45 CFR Part 46) and provides an overview of relevant OHRP guidance
regarding each required element.
Target Audience: This document primarily is intended to assist IRB
administrators, IRB chairpersons, and other relevant institutional officials
who may be responsible for preparing and maintaining written IRB procedures.
OHRP frequently receives requests for
guidance and clarification regarding the content of written IRB procedures.
In order to assist institutions in developing adequate written IRB
procedures, OHRP has compiled the following summary of the relevant
regulatory requirements and guidance issued routinely by OHRP over the past
OHRP has not developed a model written IRB
procedures document for institutions to adapt because procedures
appropriately can vary significantly among institutions as the result of
differences in institution size, the type of research activities, institutional
administrative practices, number of IRBs, and local
and state laws and regulations. For each required element, the written IRB
procedures should provide sufficient step-by-step operational details so that
an independent observer can understand how an IRB operates and conducts its
HHS regulations at 45 CFR 46.103(b)(4) and
(5) require that institutions have written IRB procedures for each of the
(1) The procedures which the IRB will
follow for conducting its initial review of research.
(2) The procedures which the IRB will
follow for conducting its continuing review of research.
(3) The procedures which the IRB will
follow for reporting its findings and actions to investigators and the
(4) The procedures which the IRB will
follow for determining which projects require review more often than
(5) The procedures which the IRB will
follow for determining which projects need verification from sources other
than the investigators that no material changes have occurred since previous
(6) The procedures which the IRB will
follow for ensuring prompt reporting to the IRB of proposed changes in a
research activity, and for ensuring that such changes in approved research,
during the period for which IRB approval has already been given, may not be
initiated without IRB review and approval except when necessary to eliminate
apparent immediate hazards to the subject.
(7) The procedures for ensuring prompt
reporting to the IRB, appropriate institutional officials, any Department or
Agency head, and OHRP of: (a) any unanticipated problems involving risks to
subjects or others; (b) any serious or continuing noncompliance with 45 CFR
Part 46 or the requirements or determinations of the IRB; and (c) any
suspension or termination of IRB approval.
GUIDANCE ON OPERATIONAL DETAILS
Written IRB procedures should provide a
step-by-step description with key operational details for each of the above
procedures. Important operational details for the above procedures should
(1) A description of any primary reviewer
system used for initial review, continuing review, review of protocol
changes, and/or review of reports of unanticipated problems involving risks
to subjects or others or of serious or continuing noncompliance.
(2) Lists of specific documents
distributed to primary reviewers (if applicable) and to all other IRB members
for initial review, continuing review, review of protocol changes, and review
of reports of unanticipated problems involving risks to subjects or others or
of serious or continuing noncompliance.
(3) Details of any process (e.g., a
subcommittee procedure) that may be used to supplement the IRBís initial review, continuing review, review of
protocol changes, and/or review of reports of unanticipated problems
involving risks to subjects or others or of serious or continuing
(4) The timing of document distribution
prior to IRB meetings.
(5) The range of possible actions taken by
the IRB for protocols undergoing initial or continuing review and protocol
changes undergoing review.
(6) A description of how expedited review
is conducted and how expedited approval actions are communicated to all IRB
(7) A description of the procedures for:
(a) communicating to investigators IRB action regarding proposed research and
any modifications or clarifications required by the IRB as a condition for
IRB approval of proposed research; and (b) reviewing and acting upon
(8) A description of which institutional
office(s) and official(s) are notified of IRB findings and actions and how
notification to each is accomplished.
(9) A description, if applicable, of which
institutional office(s) or official(s) is responsible for further review and
approval or disapproval of research that is approved by the IRB. Please note
that, in accordance with HHS regulations at 45 CFR 46.112, no other
institutional office or official may approve research that has not been
approved by the IRB.
(10) A specific procedure for how the IRB
determines which protocols require review more often than annually, including
specific criteria used to make these determinations (e.g., an IRB may set a
shorter approval period for high-risk protocols or protocols with a high risk:potential benefit ratio).
(11) A specific procedure for how the IRB
determines which projects need verification from sources other than the
investigators that no material changes have occurred since previous IRB
review, including specific criteria used to make these determinations (e.g.,
such criteria could include some or all of the following: (i) randomly selected projects; (ii) complex projects
involving unusual levels or types of risk to subjects; (iii) projects
conducted by investigators who previously have failed to comply with the
requirements of the HHS regulations or the requirements or determinations of
the IRB; and (iv) 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).
(12) A description of what steps are taken
to ensure that investigators do not implement any protocol changes without
prior IRB review and approval, except when necessary to eliminate apparent
immediate hazards to subjects (e.g., this might be addressed through training
programs and materials for investigators, specific directives included in
approval letters to investigators, and random audits of research records).
(13) A description of which office(s) or
institutional official(s) is responsible for promptly reporting to the IRB,
appropriate institutional officials, any supporting Agency or Department
heads, and OHRP any (i) unanticipated problems
involving risks to subjects or others; (ii) any serious or continuing
noncompliance with 45 CFR Part 46 or the requirements or determinations of
the IRB; and (iii) any suspension or termination of IRB approval.
(14) A description of the required time
frame for accomplishing the reporting requirements in the preceding
(15) The range of possible actions taken
by the IRB in response to reports of unanticipated problems involving risks
to subjects or others or of serious or continuing noncompliance.
ADDITIONAL OHRP GUIDANCE RELEVANT TO
WRITTEN IRB PROCEDURES
A. Guidance Relevant to Initial and
(1) Requirement for Review of Research
by the IRB at Convened Meetings. In accordance with HHS regulations at 45
CFR 46.108(b), initial and continuing reviews of research must be conducted
by the IRB at convened meetings at which a majority of the members of the IRB
are present, including at least one member whose primary concerns are in
nonscientific areas (i.e., a quorum), except where expedited review is
appropriate under HHS regulations at 45 CFR 46.110(b)(1) for the
categories of research listed in the Federal Register of November 9, 1998
(see 63 FR 60364-60367 at http://www.hhs.gov/ohrp/humansubjects/guidance/expedited98.htm).
Approval of research is by a majority vote of this quorum. Should the quorum
fail during a meeting (e.g., loss of a majority through recusal
of members with conflicting interests or early departures, or absence of a
nonscientist member), the IRB may not take further actions or votes unless
the quorum can be restored.
(2) Research Review Materials
(a) Initial Review Materials. HHS
regulations at 45 CFR 46.111 set forth the criteria that must be satisfied in
order for the IRB to approve research. These criteria include, among other
things, determinations by the IRB regarding risks, potential benefits,
informed consent, and safeguards for human subjects. In conducting the
initial review of proposed research, IRBs must
obtain information in sufficient detail to make the determinations required
under HHS regulations at 45 CFR 46.111. Materials should include
the full protocol, a proposed informed consent document, any relevant grant
application(s), the investigator's brochure (if one exists), and any
recruitment materials, including advertisements intended to be seen or heard
by potential subjects. Furthermore, for HHS-supported multicenter
clinical trials, the IRB should receive and review a copy of the HHS-approved
sample informed consent document and the complete HHS-approved protocol, if
they exist. Unless a primary reviewer system is used, all members should
receive a copy of the complete documentation. These materials should be
received by members sufficiently in advance of the meeting date to allow
review of this material.
If the IRB uses a primary reviewer system,
the primary reviewer(s) should do an in-depth review of all pertinent
documentation (see previous paragraph). All other IRB members should at least
receive and review a protocol summary (of sufficient detail to make the
determinations required under HHS regulations at 45 CFR 46.111),
the proposed informed consent document, and any recruitment materials,
including advertisements intended to be seen or heard by potential subjects.
In addition, the complete documentation should be available to all members
(b) Continuing Review Materials.
Continuing review of research must be substantive and meaningful. The IRB
must ensure that the criteria set forth by HHS regulations at 45 CFR 46.111
are satisfied at the time of continuing review. The procedures for continuing
review by the convened IRB may include a primary reviewer system.
In conducting continuing review of
research not eligible for expedited review, all IRB members should at least
receive and review a protocol summary and a status report on the progress of
the research, including: (i) the number of subjects
accrued; (ii) a summary of adverse events and any unanticipated problems
involving risks to subjects or others and any withdrawal of subjects from the
research or complaints about the research since the last IRB review; (iii) a
summary of any relevant recent literature, interim findings, and amendments
or modifications to the research since the last review; (iv) any relevant
multi-center trial reports; (v) any other relevant information, especially
information about risks associated with the research; and (vi) a copy of the
current informed consent document and any newly proposed consent document.
At least one member of the IRB (i.e., a
primary reviewer) also should receive a copy of the complete protocol
including any modifications previously approved by the IRB. Furthermore, upon
request, any IRB member
s also should have access to the complete IRB
protocol file and relevant IRB minutes prior to or during the convened IRB
The minutes of IRB meetings should
document separate deliberations, actions, and votes for each protocol
undergoing continuing review by the convened IRB.
When reviewing research under an expedited
review procedure, the IRB Chair (or designated IRB member(s)) should receive
and review all of the above-referenced documentation, including the complete
(3) IRB Review in Emergency Situations.
HHS regulations do not permit human subject research activities to be
started, even in an emergency, without prior IRB review and approval (see
45 CFR 46.103(b) and 46.116(f) and OHRP guidance at http://www.hhs.gov/ohrp/humansubjects/guidance/hsdc91-01.htm).
When emergency medical care is initiated without prior IRB review and
approval, the patient may not be considered a research subject under 45 CFR Part 46. Such emergency care may not be
claimed as research, nor may any data regarding such care be included in any
report of a prospectively conceived research activity. When emergency care
involves investigational drugs, devices, or biologics, U.S. Food and Drug
Administration (FDA) requirements must be satisfied.
(4) "Conditional" Approvals.
Convened IRBs often set conditions under which a
protocol can be approved. OHRP recommends the following guidelines in such
cases: (a) When the convened IRB requests substantive clarifications or
modifications regarding the protocol or informed consent documents that are
directly relevant to the determinations required by the IRB under HHS
regulations at 45 CFR 46.111, IRB approval of the proposed research should be
deferred, pending subsequent review by the convened IRB of responsive material.
(b) Only when the convened IRB stipulates specific revisions requiring
simple concurrence by the investigator may the IRB Chair or another IRB
member designated by the Chair subsequently approve the revised research
protocol on behalf of the IRB under an expedited review procedure.
(5) Conflicting Interest. HHS
regulations at 45 CFR 46.107(e) stipulate that no IRB member may participate
in the IRBís initial or continuing review of a
project in which the member has a conflicting interest, except to provide
information requested by the IRB. OHRP recommends that except when requested
by the IRB to be present to provide information, IRB members absent
themselves from the meeting room when the IRB reviews research in which they
have a conflicting interest, and such should be noted in the IRB meeting
(6) Initial and Continuing Expedited
Review. OHRP recommends that documentation for initial and continuing
reviews conducted under an expedited review procedure include: (a) the
specific permissible categories (see 63 FR 60364-60367 at http://www.hhs.gov/ohrp/humansubjects/guidance/expedited98.htm)
justifying the expedited review; and (b) documentation of the review and
action taken by the IRB chairperson or designated reviewer and any findings
required under the HHS regulations.
B. Guidance Relevant to IRB Records and
(1) IRB Protocol Records. IRB
protocol records must include all the information stipulated by HHS
regulations at 45 CFR 46.115(a)(1), (3),
(4), and (7).
(2) Minutes of IRB Meetings. The
minutes of IRB meetings must include all the information stipulated by HHS
regulations at 45 CFR 46.115(a)(2). The
minutes of IRB meetings should document, among other things:
(a) Separate deliberations, actions, and
votes for each protocol undergoing initial or continuing review by the
(b) The vote on all IRB actions including
the number of members voting for, against, and abstaining. In order to
document the continued existence of a quorum, OHRP recommends that votes be
recorded in the minutes using the following format: Total = 15; Vote: For-14,
(3) Documentation of Findings. HHS
regulations at 45 CFR 46.116(d) require that the IRB make and document four
findings when approving a consent procedure which does not include, or which
alters, some or all of the required elements of informed consent or when
waiving the requirement to obtain informed consent. OHRP recommends that when
approving such a waiver for research reviewed by the convened IRB, these
findings be documented in the minutes of the IRB meeting, including protocol-specific
information justifying each IRB finding.
Similarly, where HHS regulations require
specific findings on the part of the IRB, such as (a) approving a procedure
which waives the requirement for obtaining a signed consent form [see 45 CFR
46.117(c)]; (b) approving research involving pregnant women, human fetuses,
or neonates (see 45 CFR 46.204-207); (c) approving research involving
prisoners (see 45 CFR 46.305-306); or (d) approving research involving
children (see 45 CFR 46.404-407), the IRB should document such findings. OHRP
recommends that for research approved by the convened IRB, all required
findings be fully documented in the minutes of the IRB meeting, including protocol-specific
information justifying each IRB finding.
For research reviewed under an expedited
review procedure, these findings should be documented by the IRB Chairperson
or other designated reviewer elsewhere in the IRB record.
(4) Documentation of Risk and Approval
Period. IRBs must determine which protocols
require continuing review more often than annually, as appropriate to the
degree of risk [see 45 CFR 46.103(b)(4) and 46.109(e)].
OHRP recommends that the minutes of IRB meetings clearly reflect these
determinations regarding risk and approval period (review interval).
(5) Retention of IRB Records. HHS
regulations at 45 CFR 46.115(b) require that IRB records be retained for at
least 3 years, and records relating to research which is conducted be
retained for at least 3 years after completion of the research. All records
must be accessible for inspection and copying by authorized representatives
of HHS at reasonable times and in a reasonable manner.
C. Guidance Relevant to Review of
(1) Requirement for Review of Proposed
Protocol Changes by the IRB at Convened Meetings. In accordance with HHS
regulations at 45 CFR 46.108(b), review of proposed protocol changes must be
conducted by the IRB at convened meetings at which a majority of the members
of the IRB are present, including at least one member whose primary concerns
are in nonscientific areas, except where expedited review is appropriate
under HHS regulations at 45 CFR 46.110(b)(2).
(2) Expedited Review of Minor Changes.
OHRP recommends that institutions adopt policies describing the types of
minor changes in previously approved research which can be approved under an
expedited review procedure in accordance with HHS regulations at
45 CFR 46.110(b)(2).
(3) Protocol Revisions. OHRP
recommends that each revision to a research protocol be incorporated into the
written protocol. This practice ensures that there is only one complete
protocol with the revision dates noted on each revised page and the first
page of the protocol itself. This procedure is consistent with the procedure
used for revised and approved informed consent documents which then supersede
the previous one.
D. Miscellaneous Guidance
(1) Procedures for Determining
Exemptions. OHRP recommends that institutions adopt clear procedures
under which the IRB (or some authority other than the investigator)
determines whether proposed research is exempt from the human subjects
regulations [see 45 CFR 46.101(b)]. Documentation should include
the specific category justifying the exemption.
(2) Informed Consent Documents:
Approval and Expiration Dates. OHRP recommends that IRBs
affix the approval and expiration dates to all approved informed consent
documents and stipulate that copies of these dated documents must be used in
obtaining consent. This procedure helps ensure that only the current,
IRB-approved informed consent documents are presented to subjects and serves
as a reminder to the investigators of the need for continuing review.
(3) Applicability of State and Local
Laws to HHS-Supported Research. The HHS regulations do not affect any
applicable State or local laws or regulations which provide additional
protections for human subjects [see 45 CFR 46.101(f)]. OHRP
recommends that written IRB procedures describe applicable State and local
laws and regulations relevant to the conduct of human subject research.
(4) Additional Considerations.
Institutions may wish to consider including additional pertinent information
in their written IRB procedures, such as the following: (a) important
definitions (e.g., the definition of research, human subject, and minimal
risk); (b) a description of procedures for implementing other relevant
Federal regulations that apply to human subject research (e.g., FDA and HIPAA
regulations); (c) procedures for selecting and appointing the IRB chairperson
and members in order to satisfy the requirements of HHS regulations at 45 CFR
46.107; (d) procedures for training and educating IRB members and staff and
investigators; (e) a description of the required elements of informed consent
and criteria for waiving or altering these requirements; and (f) procedures
for ensuring that the IRB possesses sufficient knowledge of the local