|NOTE: THIS GUIDANCE HAS BEEN REPLACED BY OHRPíS
JULY 11, 2002 GUIDANCE ENTITLED, "GUIDANCE ON WRITTEN IRB
HERE FOR THE JULY 11, 2002 GUIDANCE.
Office for Human Research Protections (OHRP)
Department of Health and Human Services
OHRP Guidance on Written IRB
Date: April 2, 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 several years.
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 major functions.
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 annually.
(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 IRB review.
(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
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 include:
(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
(4) The timing of document distribution prior to
(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
(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 investigatorsí responses.
(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
(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
A. Guidance Relevant to Initial and Continuing
(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
(a) Initial Review Materials. 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 for review.
(b) Continuing Review Materials.
Continuing IRB review of research must be substantive and
meaningful. 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 any adverse events or
unanticipated problems involving risks to subjects or others and
of 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, findings obtained thus far,
amendments or modifications to the research since the last review,
any relevant multi-center trial reports, and any other
relevant information, especially information about risks
associated with the research; and (iv) a copy of the current
informed consent document.
Primary reviewer systems may be employed, so
long as the full IRB receives the above information. Primary
reviewers should also receive a copy of the complete protocol
including any modifications previously approved by the IRB (see
OHRP guidance at http://archive.hhs.gov/ohrp/humansubjects/guidance/hsdc95-01.htm
Furthermore, the minutes of IRB meetings
should document separate deliberations, actions, and votes for
each protocol undergoing continuing review by the convened IRB.
When conducting research under an expedited
review procedure, the IRB Chair (or designated IRB member(s))
should receive and review all of the above referenced
(3) IRB Review in Emergency Situations.
HHS regulations do not permit 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. 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 minutes.
(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://archive.hhs.gov/ohrp/humansubjects/guidance/hsdc91-01.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.
(7) Inclusion of Women and Minorities in
Research. Institutions have a responsibility to create an
environment in which equitable selection of research participants is
fostered. IRBs should specify that NIH-supported investigators provide
details of the proposed involvement of humans in the research,
including the characteristics of the subject population, anticipated
numbers, age ranges, and health statuses. The proposed research should
specify the gender and racial/ethnic composition of the subject
population, as well as criteria for inclusion or exclusion of any
subpopulation. If ethnic, racial, and gender estimates and continuing
review numbers are not included in the background data for a protocol,
the investigators must provide a clear rationale for exclusion of this
information (see OHRP guidance at http://archive.hhs.gov/ohrp/humansubjects/guidance/hsdc94-01.htm
Section 492B of the Public Health Service Act, and NIH Guide for
Grants and Contracts, Vol.23, Number 11, March 18, 1994).
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, Opposed-0, Abstained-1.
(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
C. Guidance Relevant to Review of Protocol Changes
(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
(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
(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 research context.