Protocol Review - Lab Animal 30(6), 2001

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