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Office of Laboratory Animal Welfare
Protocol Review
Jerald Silverman, DVM, Column Coordinator
Is Ad Hoc Approval Enough?
Being fairly new at Great Eastern University and fresh out of a
laboratory animal medicine residency program, Dr. Max Redding didn’t
want to upset the IACUC. He also didn’t want to get a reputation as
a pushover. Redding had previously sat in on IACUC meetings, but
this was the first one in which he was serving as the Committee’s
Veterinarian. While he was a little nervous, he tried his best to
hide it.
The first protocol was approved with minimal comments, but the
next presented a problem. An investigator proposed to use rats in a
study requiring a major surgical procedure. Redding had met with the
investigator two weeks earlier and had indicated that the
anesthetics and analgesics proposed for use were, in his opinion,
inappropriate. He had given the investigator a list of acceptable
alternatives and thought he had an agreement that the new drugs
would be used. Unfortunately, on the IACUC protocol form that was
being discussed, the original drugs were still there, but with
slightly higher dosages. The investigator was a full professor and
he was sitting in the room, answering some questions about the
protocol. When the Chair turned to Redding and asked for his
comments, Redding’s face flushed and his voice cracked, but he
managed to get out his concerns. The investigator, in a very
articulate manner, told Redding and the rest of the Committee that
the drugs he was using were previously approved by the IACUC for the
exact same procedure and he never had any problem using them. The
Chair saw that Redding was becoming more and more uncomfortable. He
thanked the investigator for his time and asked him to leave the
room while the IACUC deliberated. He then turned to Redding, calmly
suggested that it was possible that the IACUC had overlooked some
issues in the past, and asked him to support his remarks with facts.
Redding relaxed, if just a little, and gave the IACUC the rationale
behind his comments, which detailed why the previously approved
drugs provide relatively poor anesthesia and analgesia for the
proposed study. To his great surprise, the IACUC seemed to agree
with him.
A motion was made to have the Chair ad hoc approve the protocol
if the investigator would properly address Redding’s concerns. Once
again, Redding’s face flushed. Somewhat hesitatingly, he said that
this was an issue of animal welfare, not an administrative issue,
and he didn’t think that the Chair alone could approve such changes.
The Chair was a little annoyed, but agreed to let Redding review the
investigator’s response. If Redding was happy, the Chair would then
ad hoc approve the protocol. Did the Chair act appropriately in
allowing Redding, rather than the entire IACUC, to have the final
approval on the anesthesia and analgesia regimen and then,
indirectly, the protocol’s approval? Can a Chair ad hoc approve this
or any other protocol that requires an investigator to provide
answers to more than administrative questions about animal health or
well-being?
Only with the Appropriate Expertise H. Hugh Harroff, DVM
In my experience serving as a Member and working with IACUCs, it
is not at all uncommon for the Committee to approve a protocol with
contingencies. Such action, by definition, means that if the
contingencies established by the IACUC are satisfied, the Committee
approves the protocol, and the study may proceed. An important
aspect of approval with contingencies is the necessity for the IACUC
to decide who must be responsible to ensure that the contingencies
are satisfied. IACUCs may decide that all Members must review the
responses to the contingencies, a Subcommittee can review them on
behalf of the entire IACUC, or only one or two individuals can act
on behalf of the Committee. The IACUCs with which I have been
associated, by policy, vest the authority in the IACUC Chair and one
other individual. In this system, the second individual usually has
particular expertise in the area being questioned (e.g., a surgeon
if some part of a surgical procedure is in question, or the
Attending Veterinarian if some area of animal care or use is in
question). It is even the prerogative of the IACUC to call on
individuals with special expertise outside the Committee or outside
the institution if it is questioning a part of the protocol and
wants to require consultation with an outside individual as a
contingency for approval. It is the IACUC Chair and the individual
chosen for his or her expertise, who decide when the contingencies
have been satisfied, thereby approving the protocol and allowing the
study to begin.
In the situation at Great Eastern, I believe the IACUC Chair
acted appropriately in allowing Redding to review and approve the
anesthesia and analgesia on the protocol in question. It seems
obvious that Redding has expertise in the area, that he was not
satisfied with the analgesia and anesthesia as written, and that the
IACUC Members were in agreement with him and had faith in his
judgment. In my opinion, the IACUC should have made it part of the
contingency for approval that Redding and the Chair both be
satisfied with the investigator’s response with regard to analgesia
and anesthesia. Can a Chair ad hoc approve a protocol when an
investigator is asked to provide answers to more than administrative
questions? In my opinion, the Chair has such power of approval if
the IACUC sees fit to grant it. Nevertheless, I have never known of
an IACUC that gave that kind of approval power to the Chair, and I
think an IACUC would be ill advised to do so. In addition, an IACUC
Chair would be courting disaster by attesting that investigators
have satisfied contingencies in areas in which the Chair has little
or no expertise. In short, it is perfectly acceptable for an IACUC
to vest a group of two or three Members and consultants with the
authority to verify that investigators have appropriately responded
to contingencies, and thereby give final approval to a protocol. The
IACUC, however, must ensure that individuals with the expertise
needed to make a proper judgment are included in the small group.
IACUCs have myriad experts available as Members or as consultants,
and they never hesitate to use them when there is a legitimate
question or difference of opinion about a protocol.
Harroff is Chief, Operations Flight, 59th Research Squadron,
Wilford Hall Medical Center, Lackland AFB, TX.
Remember the Role of the Attending Veterinarian Tamara L.
Goodman, RVT
I am making the following assumptions: Redding is a recently
appointed voting Member of the IACUC, and an investigator should
always address the IACUC Veterinarian’s recommendations.
Furthermore, according to PHS Policy, “Procedures that may cause
more than momentary or slight pain…will be performed with
appropriate sedation, analgesia, or anesthesia, unless the procedure
is justified for scientific reasons in writing by the investigator.”
If the investigator provides scientific justification and Redding
continues to strongly oppose the analgesia and anesthesia, and the
IACUC approves the protocol without his concurrence, he may submit a
minority report to the Institutional Official. The Attending
Veterinarian (AV) should have final approval of issues directly
dealing with animal health and well-being, but, depending on an
institution’s philosophy, this may not be the case, and the IACUC
can overrule the AV’s recommendations.
The investigator obviously did not consider the scientific merit
of the AV’s recommendations. In fact, he disregarded the
Veterinarian’s recommendations by increasing the dosage. He may have
done so because he was a full professor, believing he outranked
Redding. He also may have reacted in this manner because Redding was
comparatively new to the University, had recently completed the lab
animal residency program, and Redding’s predecessor had approved the
prior anesthetic/analgesic regimen. Redding’s justification for a
different anesthetic/analgesic regimen is strong. If the previously
approved regimen provides relatively poor anesthesia and analgesia
for the major surgical procedure, alternative drugs must be used. As
stated in the Guide for the Care and Use of Laboratory Animals, “The
veterinarian must provide guidance to investigators…in the care and
use of animals to ensure appropriate…analgesia [and] anesthesia. An
integral component of veterinary medical care is prevention or
alleviation of pain associated with…surgical protocols.”
Despite past approval, the investigator’s anesthetic/analgesic
regimen may not meet today’s standards. This is a common problem
that IACUCs need to address. The IACUC Chair appears to undervalue
Redding’s role in the protocol-approval process. According to PHS
Policy, the AV has the authority to oversee the adequacy of animal
care and use. Redding is responsible for the care of the rats,
including the anesthetics and analgesics used. The IACUC Chair may
not be qualified to approve the anesthetic/analgesic regimen in the
revised protocol; thus, Redding should approve of the revision
before the Committee approves the protocol.
Did the Chair act appropriately in allowing Redding, rather than
the entire IACUC, to have the final approval on the anesthesia and
analgesia regimen and then, indirectly, the protocol’s approval?
Yes. The AV must ensure the anesthesia and analgesia regimens are
appropriate. By approving a motion to let the Chair administratively
approve the protocol after the investigator submitted revisions, the
Committee, in essence, approved a designated review.
Can a Chair ad hoc approve this or any other protocol that
requires an investigator to provide answers to more than
administrative questions about animal health or well-being? The full
Committee may have declared this protocol approved pending
clarification, in which case there would be no need for further
discussion. As stated in PHS Policy, one member of the IACUC has the
authority to approve the protocol if the Committee does not request
full review. This person must be qualified and appointed by the
Chair or, in this case, be the Chair himself. If Redding is a voting
member of the IACUC and he disagrees with the Chair’s decision, he
may call for full review or may submit a minority report.
Goodman is IACUC Program Director, University of Cincinnati,
Cincinnati, OH.
Ad Hoc Is Not Appropriate Laurie M. Serfilippi, VMD
In accordance with the Animal Welfare Act Regulations
2.31(d)(xi)(2), prior to IACUC review, each Member of the Committee
shall be provided with a list of proposed activities to be reviewed.
Written descriptions of all proposed activities that involve the
care and use of animals must be available to all IACUC Members, and
any Member of the IACUC may obtain, on request, full Committee
review of those activities. In light of this statement, unless all
IACUC members had agreed to allow Redding to have final approval, it
is inappropriate for the Chair to allow the Committee’s Veterinarian
to have final approval on the anesthesia and analgesia regimen and,
indirectly, the protocol’s approval. All Committee Members need to
review the investigator’s answers to the anesthesia/analgesia
questions and make their own decisions as to whether the answers are
acceptable. With this information, the Committee Members can decide
whether a designated reviewer can approve the protocol and sign off
on it; any one Member can then call for a full Committee review if
he or she believes that further clarification is needed.
In general, it is the AV’s position to advise the Committee
Members on the proper treatment of animals—be it anesthesia,
analgesia, handling, husbandry, restraint, etc. It is not the
Veterinarian’s role to make these decisions for the Committee.
Apparently, Redding provided the Committee Members with convincing
information on the appropriate anesthetics and analgesics to use on
rats. The Committee seemed to agree with him at the end of his
presentation, but this does not mean that they would not agree with
a response presented by the investigator that scientifically
justified an anesthetic/analgesic technique that differed from the
one suggested by Redding. Therefore, all Committee Members need to
review the response given by the investigator, since the Committee
did not agree at the full IACUC meeting on a definite course of
action to be taken; they only “seemed” to agree with the
Veterinarian’s choice of anesthetics and analgesics.
In general, the Chair cannot ad hoc approve a protocol that
requires an investigator to provide answers to questions concerning
animal health or well-being. All Committee Members need to review
these answers and either agree with them or have the opportunity to
call a full Committee meeting if they believe that further
discussion of the issues is warranted. The only exception to this
rule that may be allowable is if, at the IACUC meeting, definite
changes that all Committee Members agreed upon and approved were
made and documented in the minutes. The investigator would then
incorporate these changes in the protocol just as the Committee
Members had set forth at the IACUC meeting. At this point, a
designated member—in this case, the Chair—could then give the
protocol final approval and sign off on it.
Goodman is IACUC Program Director, University of Cincinnati,
Cincinnati, OH.
A Word From OLAW and USDA
In response to the two specific questions posed in this scenario,
the Office of Laboratory Animal Welfare (OLAW) and United States
Department of Agriculture (USDA) offer the following clarification
and guidance:
The first question asks whether the Chair acted appropriately in
allowing Redding, rather than the entire IACUC, to have the final
approval on the anesthesia/analgesia regimen and then, indirectly,
the protocol’s approval. It is completely appropriate for the IACUC
to rely on the professional judgment of the Veterinarian in the
approval of the anesthesia/analgesia regimen. The Veterinarian has a
special role outside of his duties as an IACUC member. There is an
explicit requirement for consultation with the Veterinarian
regarding appropriate anesthesia/analgesia during the planning
stages of projects involving surgery; this consultation ordinarily
occurs prior to the IACUC review process. In addition, the
Veterinarian has the obligation to provide guidance to investigators
on the appropriate choice of anesthetics and analgesics, and is
generally responsible for the program of adequate veterinary
care.
The Public Health Service (PHS) Policy and the USDA Animal
Welfare Act (AWA) regulations require that pain and distress be
limited to that which is unavoidable in the conduct of valuable
research. Therefore, it would be inappropriate for the IACUC to
approve a proposal where the above conditions have not been met.
The Veterinarian, as an IACUC Member, may be designated final
approval authority in accordance with IV, C, 2. of the PHS Policy
and Paragraph 2.31(d)(2) of the USDA regulations regarding
designated review. This assumes it is clear to the Committee that
they are switching to designated reviewer mode for final approval
and that no Member of the Committee specifically requests approval
be granted only by the full Committee review process.
The second question asks whether a Chair can ad hoc approve this
or any other protocol that requires an investigator to provide
answers to more than administrative questions about animal health or
well-being. This question begs a definition of “ad hoc approval,”
and what kinds of issues might be dealt with administratively,
versus through a full Committee or designated review process.
The Chair may qualify as a designated reviewer, and in that
capacity could review and approve the entire proposal or the
response to required changes, as long as the explicit federal
requirements for review are followed.
It is possible for proposals to be approved pending receipt of
certain information of a purely administrative nature, that is,
involving matters unrelated to the substantive deliberations and
judgments of the IACUC (e.g., the provision of a current phone
number). Other, more substantive “conditions” of approval may be so
clear-cut as to require only verification that they have been met
(e.g., approval pending verification that the work will be conducted
in a hood). Responses to requests for such information or
verification may be handled administratively without a requirement
for further formal IACUC review.
On the other hand, IACUC requests for substantive information
requiring further deliberation or IACUC judgment must be handled
using one of the two recognized methods of review (i.e., “full” or
“designated member” review). OLAW and the USDA have provided
previous guidance on this subject, which may be found at:
http://www.labanimal.com/col/prot0898.htm.
Nelson L. Garnett, DVM Director, Office of Laboratory Animal
Welfare National Institutes of Health W. Ron DeHaven,
DVM Deputy Administrator USDA, APHIS, Animal Care
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