Protocol Review - Lab Animal 27(8), 1998

Lab Animal 27(8), 1998

So Much Work, So Little Time

The Great Eastern University IACUC members often complained that the committee’s work took up far too much of their time. The chair, Don Montagna, was sympathetic because he estimated that IACUC work took about a third of his own time, in addition to his full research and teaching load.

The IACUC secretary, Linda Fasulo, came up with a time-saving suggestion that was satisfactory to everyone. Under the usual operating procedure, responses to requested clarifications of protocols under review routinely went back to Montagna and those committee members who requested the clarifications. Once they all approved the clarifications, they recommended approving the protocol at the next full IACUC meeting. Fasulo suggested modifying the process so that only the chair need approve the submitted clarifications. That way, the IACUC members who requested the clarifications save time; the IACUC chair does not spend any additional time; and the full committee need only give a "rubber stamp" approval of the protocol. The IACUC passed the suggestion unanimously, with the caveat that if the chair was not fully satisfied with an investigator’s response, he would consult with the members who requested the clarification.

This system worked well for the IACUC. Montagna evaluated requested clarifications, and, if everything was in order, he told Fasulo to send an approval letter to the investigator. At the next IACUC meeting, the full committee voted official approval of the protocol. At one meeting, however, everything did not go so well. The attending veterinarian (AV) asked that the IACUC not approve a protocol because the investigator required more rodent surgical training. Montagna, somewhat confused by this, reiterated the new IACUC policy. He said that the investigator had properly responded to the concerns of the committee (which did not include further surgical training), had already received the approval letter, and had already begun the study.

The AV was not happy, and did not mince his words. He said that the investigator was training for surgery when he submitted the protocol, and, although it seemed at that time that he was making reasonable progress, the investigator still needed more experience. The AV made it clear that, as per the AWA Regulations and PHS Policy, the IACUC as a whole—not just the chair—had to approve each protocol by vote. Since the IACUC only delegated to the chair the authority to review the responses from the investigator and then make a recommendation to the full committee, the approval letter would not be effective until the full committee voted approval.

Montagna felt the AV was absolutely wrong. The entire committee already had the opportunity to read and discuss the protocol. The members had delegated to the chair the authority to approve the protocol if appropriate corrections were made. Montagna told the AV that he had acted within the spirit and letter of PHS Policy and AWA Regulations, and that the procedure was not substantially different than an expedited protocol review. The AV countered with the question, "If you have the authority to approve the protocol based on the requested clarifications, why does the IACUC always vote on the protocol at its next meeting?" Montagna replied that the vote is a mere formality to show that he reviewed and approved the changes to the protocol, and is not actually necessary for approval.

The committee members wanted an answer, not a debate. What is the resolution to the immediate problem at hand? How can future problems be avoided?


Be More Thorough

Richard M. Harrison, PhD

The IACUC took an important, time-saving step by changing its procedure for approving protocols requiring clarification. In this particular case, the committee erred in not being thorough enough in its initial review.

The AV was correct that the IACUC, as a whole, has to vote for approval; and, if an investigator is not adequately trained for a protocol requiring surgery, a project should not begin. Montagna, on the other hand, was also correct that the IACUC had followed policy, did have the opportunity to review the protocol, and had voted to approve pending acceptable clarification.

The Guide states, "It is an institutional obligation to ensure..." that an investigator be qualified to perform protocol-required surgery. The AV was aware that the investigator had not completed training, and should have made that clear at the initial protocol review. The IACUC could have then approved the protocol contingent on acceptance of clarifications and completion of the investigator’s surgical training. The secretary would send a final approval letter only when the AV and IACUC were satisfied that training was complete and requested clarifications met.

One might consider the second, "official" vote as notification that the IACUC had received clarifications and had confirmed the initial vote. If, however, Montagna was aware that investigator training was in progress at the time of initial protocol review, he should have checked with the AV to confirm training completion before sending the final approval letter.

At this point, the IACUC has the right, according to PHS Policy, to "suspend a previously approved activity involving animals if it is determined that the activity is not being conducted in accordance with…the Guide." The IACUC’s incomplete initial review does not justify allowing a project to continue with an untrained investigator performing surgery. The committee could allow the project to continue, however, if the AV agreed to assist the investigator, providing both the required experience and on-the-job training.

The IACUC may not assume that training is completed, the facility renovated, or any other factors affecting animal care and use. The protocol form should include a section listing all personnel involved with a project, and a signed investigator statement assuring that listed personnel have completed all training necessary for the project. The IACUC should know if physical changes in the facility are required. The contingency letter should make it clear that training and facility changes must be completed prior to final protocol approval, and the IACUC Chair should ascertain that information before sending the final approval letter.

Harrison is a research scientist, and IACUC chair, at the Tulane Regional Primate Research Center, Covington, LA.


Keep in Touch

Daniel A. Sadoff, DVM

An effective IACUC thrives on communication at many levels, no matter how large its workload or the interval between meetings. The AWA Regulations specifically allow the delegation of protocol and amendment approval to a subcommittee or individual, provided that all IACUC members have the opportunity to request full IACUC review of any protocol or modification. The IACUC chair’s decision was consistent with the AWA and with established IACUC procedure; in this case, however, better communication would have prevented a confrontation.

If the AV was concerned about the investigator’s training, he could have brought it up during the initial review, and requested that completion of the training course be a condition of protocol approval. Now that the study has started, the AV or his training coordinator can observe the investigator at work, providing assistance if needed, until the AV is satisfied with the investigator’s competence.

Many IACUCs now avoid Great Eastern’s problem by conducting most committee business by email. All IACUC correspondence can be copied automatically to every member, and the secretary can print hard copies for the files. The responsibility is thus shifted to individual members to read protocols, amendments, and clarifications, and to respond within a specified time if they have any further questions or concerns. A failure to respond within the time limit would be equivalent to accepting correspondence as written, after which the IACUC can send an approval letter to the investigator.

Sadoff is a consulting lab animal veterinarian, St. Paul, MN.


Is There Really a Problem?

Charles P. Raflo, DVM, MS

The Great Eastern IACUC is not unusual in that it feels overworked. The committee is obviously performing its duties and responsibilities in a proper manner, and is trying to set up a method by which the least number of members have to spend additional time. Neither the Guide, PHS Policy, nor the AWA Regulations tell the IACUC how to specifically carry out its functions. Each IACUC usually has an SOP that details the procedures that the committee will follow in fulfilling its charge. These procedures are normally explained in the OPRR Assurance Statement and the AAALAC International Program Description.

The solution presented in the above scenario is reasonable. A number of the IACUCs with which I have been associated have set up similar work routines. Three committees on which I currently serve permit either the chair or the veterinarian to review requested changes. The designated person evaluates the investigator’s answers, and either approves them or requests additional information. This system affects protocols that require only minor corrections or minimal additional information. These are contingency-approval protocols, approved on adequate response to the IACUC’s questions. The IACUC lists requested information item by item in a letter to the investigator, informing him or her of its action. The full IACUC does not review these protocols a second time, as the members have given a designated person permission to act in its place when evaluating requests for more information or clarification. If the answers satisfy the IACUC’s concerns, a letter of full approval with the IACUC chair’s signature is sent to the investigator.

On the other hand, PHS Policy, OPRR Assurance, and the AWA Regulations all specifically address training. These documents require that investigators and other personnel be appropriately qualified to perform their duties, and that the institution provide the necessary training. The problem above seems to stem from differing interpretations of the Policies and the AWA, as well as the IACUC’s failure to indicate in its letter to the investigator that training is a problem.

Since the investigator has already received an approval letter from the committee, either the chair or the AV should call or personally meet with the investigator and explain the situation. The AV should continue to watch and train the investigator, and report back to the committee in a reasonable amount of time (i.e., a few weeks). This would assure the AV that the investigator receives adequate training, and that the committee has carried out its duties. The IACUC could avoid future problems of this nature by assuring itself that it has covered all the required items in the protocol to everyone’s satisfaction. If the IACUC has agreed on a policy of permitting the chair to evaluate requested answers and clarification, that should be its rule of the road.

Raflo is the director, Animal Care Operations at the University of Houston, Houston, TX.


OPRR and USDA Commentary:

It is important to note that the issues discussed in this hypothetical case study are highly context-specific. Readers are cautioned not to over interpret or apply out of context the comments on this specific case. Changes in any of the assumptions or variables described will have a significant effect on the "right" answers. Although this case study may not involve USDA-covered rodents, it is important to consider how one might apply USDA requirements to a similar case involving USDA-covered species.

In its laudable efforts to reduce the burden on IACUC members and the investigator, the Great Eastern IACUC has created confusion, jeopardized animal welfare, and possibly caused the institution to be out of compliance with the PHS Policy.

The most immediate problem at hand is the welfare of the animals involved in a surgical protocol. The institution’s obligation to ensure that all individuals who care for or use animals are qualified to do so supercedes all administrative considerations. All of the respondents recognize that problem, and have provided practical suggestions on how to ensure animal welfare.

A second problem is poor communication. If the IACUC had been more explicit in its modification of procedures, it could have avoided the misunderstanding about the chair’s role in final protocol approval. The AV could and should have raised his concerns about the investigator’s surgical competence at a much earlier stage. This would have identified the completion of training as a mandatory prerequisite for approval, regardless of method.

The IACUC’s initial practice was within the bounds of the Policy and Regulations because it did not consider the protocol approved until after it underwent a final "official approval" vote by a convened quorum of the full committee. A major flaw that emerged in the modified procedure, however, was issuing premature approval letters prior to the "official approval." It was a premature approval letter that triggered the misunderstanding between the chair and the AV, and put the IACUC in the awkward position of having inadvertently approved an unqualified investigator’s protocol.

By sending out the approval letter, the chair assumed the authority to operate unilaterally in a quasi-designated reviewer mode. This authority was obviously not specified in the procedural modifications that the IACUC had approved, as evidenced by the disagreements that followed. The IACUC could have used the designated reviewer method (see below) to allow an individual member or members to make a final determination. In the event that more than one designated reviewer is involved, all designated reviewers must review and agree on any substantive modifications, even if only one designated reviewer requested them (otherwise, reviewers will be reviewing and approving protocols which are substantially different). In designated reviewer mode, however, the retroactive full-committee ratification at a subsequent meeting is irrelevant to the approval process, and unnecessarily confusing.

Protocol Review Guidance

The PHS Policy and USDA Regulations recognize only two methods of IACUC review: full-committee review by a convened quorum of the members of the IACUC; or designated member review after all members have had the opportunity to call for full-committee review.

Hybrid systems of protocol review that attempt to combine elements of full review and designated review (as in this scenario) frequently fail to fully meet the essential requirements of either method. Each of these methods has safeguards built into it which, if short-circuited via modification, it may lose. For this reason, OPRR and USDA recommend that institutions design their protocol review processes to conform as closely as possible to the PHS Policy (IV.C.2.) and USDA Regulation [9 CFR, Part 2, section 2.31(d.)(2.)] language. We encourage institutions to consult with OPRR and USDA before implementing procedural changes that may deviate from the Policy and Regulation language.

Although not specifically addressed in the Policy or Regulations, using the chair or other designated member for final review and approval of IACUC-required substantive protocol modifications or clarifications would seem acceptable, as the Policy and Regulations allow this approach for the review and approval of the entire protocol. However, IACUCs must be aware, and explicitly note, that they have shifted to the designated reviewer mode for this final stage of approval and act accordingly. Again, the retroactive full-committee ratification unnecessarily confuses the designated reviewer mode.

For PHS Policy and USDA Regulation purposes, IACUCs either approve, require modifications in (to secure approval), or withhold approval of proposals. Designated reviewers may approve, require modifications to secure approval, or request full committee review. Anything short of final approval via one of the above methods is not adequate for initiation of animal activities or submission of an IACUC approval date to NIH as part of a grant application. Further, using undefined terms such as "conditional approval," "provisional approval," or "approved pending clarification" frequently causes confusion. For this reason, OPRR and USDA recommend that IACUCs either avoid these terms, or describe them in sufficient detail to be fully understood.

IACUCs might determine that a protocol is approvable, contingent on receipt of a very specific modification (e.g., receipt of assurance that the investigator will conduct the procedure in a fume hood). The IACUC could handle these modifications or clarifications as administrative details that an individual, such as the chair, could verify. On the other hand, protocols that are missing substantive information necessary for the IACUC to make a judgement (e.g., justification for withholding analgesics in a painful procedure) are incomplete. If the protocol is incomplete, it is not possible to satisfy the first step in all protocol review processes, i.e., a complete description of the proposal and the opportunity for the entire committee to call for full review. OPRR and USDA recommend that IACUCs devise effective ways of differentiating between substantive omissions and administrative issues.

Finally, while electronic communications can substantially conserve time and material, there are certain functions that the IACUC may not conduct without a convened quorum present. For more information on this topic, review the article, "Issues for IACUCs: Use of Electronic Communications for IACUC Functions" (ILAR Journal; 37(4):190-192, 1995).

Nelson L. Garnett, DVM director, Division of Animal Welfare, OPRR, NIH.
W. Ron DeHaven, DVM, acting deputy administrator, Animal Care, USDA/APHIS


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