UAMS Human Research Advisory Committee
February 6, 2003
SUBJECT: Written Procedures Governing the
HHS regulations at 45 CFR
46.103(b)(4) and (5) require written procedures for each of the following:
Conducting initial review of research.
Conducting continuing review of research.
Reporting findings and actions to investigators and the institution.
Determining which projects require review more often than annually.
5. Determining which projects need verification from sources other than the investigators
Ensuring that no material changes have occurred since previous HRAC
Ensuring prompt reporting to the HRAC of proposed changes in a research
activity, and for ensuring that such changes in approved research, during the
period for which HRAC approval has already been given, may not be initiated
without HRAC review and approval except when necessary to eliminate apparent
immediate hazards to the subject.
8. Ensuring prompt reporting to the HRAC, 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 HRAC; and
any suspension or termination of HRAC approval.
HRAC policy 7.4)
Requirement for Review
of Research by the HRAC 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
HRAC at convened meetings at which a majority of the members of the HRAC are
present, including at least one member whose primary concerns are in
nonscientific areas (i.e., a quorum), except where expedited review is
appropriate [45 CFR 46.110(b)(1)]. Approval of research is by a
majority vote of this quorum (see
HRAC policy 3.2). 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 HRAC may not take further actions or votes unless the
quorum can be restored.
Initial Review Materials. HHS regulations at 45 CFR 46.111 set forth the criteria that must be satisfied in order for the HRAC to approve research. These criteria include determinations by the HRAC regarding risks, potential benefits, informed consent, and safeguards for human subjects. In conducting the initial review of proposed research, HRACs must obtain information in sufficient detail to make the determinations required (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.
The primary reviewer(s) should do an in-depth review of all pertinent documentation (see previous paragraph). All other HRAC members should 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.
Continuing Review (See
HRAC policy 7.6)
HRAC members should 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 HRAC 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 HRAC (i.e., a primary reviewer) also should
receive a copy of the complete protocol including any modifications previously
approved by the HRAC. Furthermore, upon request, any HRAC member
should have access to the complete HRAC protocol file and relevant HRAC minutes
prior to or during the convened HRAC meeting.
The minutes (see
HRAC policy 6.3) of HRAC meetings should document separate deliberations,
actions, and votes for each protocol undergoing continuing review by the
4. When reviewing research under an expedited review procedure, the HRAC Chair (or designated HRAC member(s)) should receive and review all of the above-referenced documentation, including the complete protocol
HRAC Review in Emergency Situations. (See HRAC policy 18.3,
research activities can not be started, even in an emergency, without prior HRAC
review and approval (see 45 CFR 46.103(b) and 46.116(f). When
emergency medical care is initiated without prior HRAC 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.
HRAC policy 7 .1)
When the convened HRAC requests substantive clarifications or modifications regarding the protocol or informed consent documents that are directly relevant to the determinations required by the HRAC under HHS regulations at 45 CFR 46.111, HRAC approval of the proposed research should be deferred, pending subsequent review by the convened HRAC of responsive material.
Only when the convened HRAC stipulates specific revisions requiring simple concurrence by the investigator may the HRAC Chair or another HRAC member designated by the Chair subsequently approve the revised research protocol on behalf of the HRAC under an expedited review procedure.
HRAC policy 3.3)
HHS regulations at 45
CFR 46.107(e) stipulate that no HRAC member may participate in the HRACís
initial or continuing review of a project in which the member has a conflicting
interest, except to provide information requested by the HRAC. OHRP recommends
that except when requested by the HRAC to be present to provide information,
HRAC members absent themselves from the meeting room when the HRAC reviews
research in which they have a conflicting interest, and such should be noted in
the HRAC meeting minutes.
Expedited Review. (See
HRAC policy 7.5)
Records and Documentation
[45 CFR 46.115(a)(1), (3), (4), and
1. Minutes of HRAC Meetings. The minutes of HRAC meetings should document, among other things:
a. Separate deliberations, actions, and votes for each protocol undergoing initial or continuing review by the convened HRAC.
The vote on all HRAC actions including the number of members voting for,
against, and abstaining. In order to document the continued existence of a
quorum, 45 CFR 46.115(a)(2)
2. Documentation of Findings. HHS regulations at 45 CFR 46.116(d) require that the HRAC make and document 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 HRAC, these findings be documented in the minutes of the HRAC meeting, including protocol-specific information justifying each HRAC finding.
Similarly, where HHS regulations require specific findings on the part of the HRAC, 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 HRAC should document such findings. OHRP recommends that for research approved by the convened HRAC, all required findings be fully documented in the minutes of the HRAC meeting, including protocol-specific information justifying each HRAC finding.
For research reviewed under an expedited review procedure, these findings should be documented by the HRAC Chairperson or other designated reviewer elsewhere in the HRAC record.
Documentation of Risk
and Approval Period. HRACs
must determine which protocols require continuing review more often than
annually, as appropriate to the degree of risk [see HRAC policy 16.1 and 45 CFR 46.103(b)(4) and
46.109(e). The minutes of HRAC
meetings should clearly reflect these determinations regarding risk and approval
period (review interval).
Retention of HRAC
Records. HHS regulations at
45 CFR 46.115(b) require that HRAC 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 (see
HRAC policy 5.1).
Review of Protocol Changes
Review of Proposed
Protocol Changes by the HRAC at Convened Meetings. In accordance with HHS regulations at 45 CFR
46.108(b), review of proposed protocol changes must be conducted by the HRAC at
convened meetings at which a majority of the members of the HRAC 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).
of Minor Changes.
Institutions should 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).
Revisions. Each revision to
a research protocol should 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.