Protocol Review - Lab Animal 27(9), 1998

The Unofficial Official?

An anonymous call to Great Eastern University’s hotline led to an unfortunate sequence of events involving its IACUC. The caller alleged that Dr. Paul Samuels, an experienced research veterinarian, was performing unauthorized surgery on calves at one of the university’s farms. The university made a preliminary investigation, verified the allegation, and determined that the surgery was related to basic medical research. When confronted with this information and asked for an explanation, Samuels readily admitted that he was performing the studies. He claimed, however, that because his work was with farm animals, it was his understanding that he did not need IACUC approval.

The IACUC met in a formal session with Samuels. It discovered that Samuels, who recently joined the university from an Australian veterinary school, had not yet attended Great Eastern’s IACUC training course. He had been performing surgeries for three months, and performing them very professionally. His academic department was aware of the work he was doing, but assumed he had IACUC approval. Samuels apologized profusely and volunteered to immediately stop his work until he completed all required university training and obtained IACUC approval.

After Samuels left the room, the IACUC Chair asked for opinions on how to resolve the matter. Some argued that there are animal care and use committees in Australia, and, as an established investigator, Samuels should have known that what he was doing was wrong. Others argued that animal welfare was not compromised; a new faculty member made an unfortunate but honest error; and, since he had agreed to halt the project and follow all university policies, the institution need not take any further action.

After some heated discussion, the majority of the IACUC agreed to suspend the project until all university requirements were met. Unfortunately, the Institutional Official (IO), who was at the meeting, was opposed to a formal suspension and the consequent notification of appropriate governmental agencies. He said Samuels’ self-imposed suspension would have the same result, and he simply would not agree to anything more. The IACUC Chair made it very clear that once the IACUC suspended the protocol, the Animal Welfare Act Regulations (AWAR) state that the IO must meet with the IACUC, take appropriate corrective action, and report the same to the federal government. He emphasized that the AWAR uses the word "shall," not "should."

The IO was equally adept at wordsmanship. He pointed out that the AWAR allows the IACUC to suspend a previously approved activity, but, since nothing had ever been approved, the IACUC had nothing to suspend. He added that he regretted this particular study had begun, and that the university and the IACUC would certainly have to quickly review the way it notifies new personnel of its animal use policies. Nevertheless, the IO felt the decision was his, not the IACUC’s. Since he was in the room and heard all sides of the issue, he would stand by his decision.

Clearly, Great Eastern has to review its policies, but is the IO on solid ground? How would you resolve this problem?

In the Spirit of the Law

Lawrence H. Herbst, DVM, PhD and Diane J. Gaertner, DVM

We believe that the IO has correctly interpreted the law: the IACUC should accept the investigator’s voluntary suspension of research activities until all required training and IACUC approvals are completed. The section of the AWAR [2.31, (c), 8] on suspension of activities involving animals refers specifically to suspension of previously approved activities. We believe this wording is intended to empower the IACUC, making it clear that "approval" is an ongoing process, not a permanent status. The spirit of the law is that regulatory bodies should be informed when major problems of humane concern occur during experimentation under an approved protocol.

Samuels made an honest error but was not intentionally noncompliant; animal suffering did not occur as a consequence of his mistake. It appears that the IACUC’s true and appropriate intent is to withhold approval of this investigator’s study until he meets all of the university’s requirements, including IACUC review. As long as Samuels stops his work as promised, withholding approval does not need to be reported to the federal government. Thus, the IACUC should accept Samuels’ voluntary cessation of work; assist him in preparing an acceptable protocol; and concentrate on ensuring that all new investigators at Great Eastern are aware of the need for IACUC approval for all species prior to initiating studies.

The IO is not intentionally concealing problems from regulatory agencies, but is rightfully concerned with avoiding negative publicity and embarrassment to the institution and the investigator. The issue, its discussion, and its resolution will be documented in IACUC minutes, semiannual program review reports, and OPRR assurance reports–all of which regulatory agencies have access to and routinely review.

One larger problem that the IACUC and the IO need to address is that there may be a systematic failure to provide timely and adequate investigator (personnel) training. If this investigator’s lack of proper information reflects a deficiency in the institution’s program for animal care and use, this should be a subject for discussion at the IACUC’s semiannual program review and its report to the IO. Further, if changes in the mechanisms of training new personnel are major changes in the program, then these should be included in the annual OPRR assurance report if the institution is NIH-funded.

Another problem is that the Regulations intend that the IO take appropriate action in consultation with the IACUC, not unilaterally. The statement, "The decision was his, not the IACUC’s" seems to violate this intent. Rather than attempt to dictate to the IACUC, the IO should convince them of the validity of his arguments by citing the text of laws and regulation so that the action he takes reflects a consensus. The IACUC and the IO need to develop and implement institutional policies together. If they fail to reach consensus and the IACUC Chair and the majority of the voting members believe the problem should be reported, they should seek a pre-report clarification from OPRR.

Herbst is affiliated with the Institute for Animal Studies and Department of Pathology, and Gaertner with the Institute for Animal Studies and Department of Microbiology and Immunology, at Albert Einstein College of Medicine, Bronx, NY.

IO OK

Daniel D. Myers, Jr, DVM and Howard G. Rush, MS, DVM

In the above scenario, the first issue to address is which regulatory agencies are involved, since the source of Samuels’ funding is not stated. If the funds are from PHS, then PHS Policy on Humane Care and Use of Laboratory Animals would apply. The IACUC could also voluntarily choose to apply PHS Policy to this case. However, if no PHS funds are involved, the IACUC would be within its rights not to report the incident to OPRR. On the other hand, since cattle are covered under the AWA Regulations when used in biomedical research, the reporting requirements under the AWA Regulations apply.

The second issue for the IACUC to address is what constitutes a suspension under the AWA Regulations and, if applied to this case, PHS Policy. Under section IV, F of PHS Policy, the IACUC must report any activity that it has suspended. Suspension is further defined in an OPRR Report (January 12, 1994) as an IACUC intervention that results in the temporary or permanent interruption of an activity involving animals. The AWA Regulations [2.31, (d), 7] state, "If the IACUC suspends an activity involving animals, the Institutional Official (IO) in consultation with the IACUC,...take appropriate corrective actions and report that action...to APHIS and any Federal agency responsible for funding that activity." However, no definition of suspension is provided in the AWA Regulations [Definitions, section 1.1] or the Animal Care Policy Manual.

The IO is correct in believing that the matter could be effectively resolved without suspending Samuels formally. In both the AWA Regulations and PHS Policy, suspension is an IACUC action. In this scenario, however, Samuels has voluntarily stopped his work pending completion of all required university training and IACUC approval. The IACUC therefore need not take further action with regard to suspension. If it takes no action to suspend the activity, the IACUC need not report it to OPRR or APHIS. It is important to note that the welfare of Samuels’ animals was not compromised, and he fully cooperated with the IACUC in resolving the issue. In this case, the IACUC would be justified in withholding approval of Samuels’ research until it has reviewed and approved a written proposal of his research activities, and he and his staff have completed Great Eastern’s IACUC training course.

Another issue to resolve is that the IO must realize that he cannot overturn a majority vote for the IACUC. It is imperative that the IO understand his role in association with the IACUC as per the AWA Regulations [2.31, (d), 8].

In this case, Samuels and his staff needed a more complete orientation to university polices and procedures. It would be beneficial for all parties concerned if, in the future, academic departments hiring new investigators who use animals notify the IACUC, so it can arrange orientation and training sessions.

Myers is a Postdoctoral Research Fellow, and Rush an Associate Professor of Laboratory Animal Medicine/Assistant Director, Unit For Laboratory Animal Medicine, with The University of Michigan, Ann Arbor, MI.

File a Report

Todd A. Jackson, DVM, dipl. ACLAM

The Great Eastern IACUC has handled the situation properly so far. It investigated the problem, met with the researcher, and stopped further activity pending investigator training and protocol approval.

Given that the IACUC is handling everything appropriately, the main issue is the IO’s reluctance to see the IACUC’s actions as a suspension of animal activities. One would assume that the IO’s stance stems from a desire to avoid tarnishing the reputation of the university and its new investigator by reporting the suspension. Unfortunately, the IO’s reluctance to fulfill his reporting responsibility is more likely to tarnish the university’s reputation.

OPRR has provided written guidance on this issue. In a "Dear Colleague" letter¹, OPRR acknowledged that IACUCs should use professional judgement in deciding which incidents to report. However, it specifically lists conduct of animal activities without IACUC review and approval as an example of an incident that should be reported. OPRR has also suggested that assured institutions should report suspensions of animal activities, even if the suspended activity is not directly PHS-funded ². The IACUC Chair should present these documents to the IO.

The IACUC Chair may also ease some of the IO’s qualms by suggesting that the investigator’s name be omitted from the report. The IO could submit a detailed report documenting the IACUC’s actions without specifically naming Samuels. It is likely that USDA and OPRR would be more concerned with how the problem was resolved than with the name of the person involved. Overall, it would be less damaging to Great Eastern’s reputation to document and report proper handling of a problem, than to have it discovered at a later date that IO ignored his responsibility to file a report.

One would also expect the IACUC to look for deficiencies in the animal care program that allowed unapproved surgeries to remain undetected for three months. How were the calves purchased? Many institutions require all animal purchases to be ordered through a central service unit so that it can verify IACUC approval before placing an order. This also simplifies tracking the number of animals the institution uses. Where were the calves housed? The manager of the animal facility should be certain that all animals are appropriately identified. The lack of a protocol number on the calves’ cage cards could have triggered someone to verify IACUC approval of the project. Where were the surgeries performed? The surgical support staff would have detected the problem early on if they had attempted to review the protocol to learn what pre-operative and post-operative care the calves would need.

References

1. OPRR Reports. January 12, 1994.
2. ILAR News; 35(3-4):47-49, 1993.

Jackson is the Associate Director of Laboratory Animal Medical Services at the University of Cincinnati, OH.

The View from USDA and OPRR

NB: The issues discussed in this hypothetical case study are highly context-specific. We caution readers 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.

Under PHS Policy and USDA Regulations, the IO is on very shaky ground. The USDA Regulations are applicable to the research because of the biomedical nature of the farm animal involvement.

The PHS Policy may be applicable to this scenario, due to direct or indirect PHS support for the project, or by voluntary inclusion in the PHS Animal Welfare Assurance of all activities involving animals, regardless of funding source. If so, the incident would include serious noncompliance with the PHS Policy and would be reportable on multiple grounds, and the issue would not be limited to the technicality of whether the IACUC action constitutes a suspension.

The most serious regulatory noncompliance in this example is the conduct of animal activities outside of all institutional oversight mechanisms. Such conduct not only leaves animals without institutional protection, it also may place the institution’s Assurance and eligibility for receiving PHS support in jeopardy.

While it is debatable whether the IACUC can technically suspend an activity that it has not previously approved, PHS Policy, USDA Regulation, and the Guide language presume that all ongoing animal activities have received prospective review and approval. Accordingly, the IACUC’s authority to suspend unauthorized activities is always implied, if not explicit.

OPRR has defined "suspension" as any IACUC intervention that results in the temporary or permanent interruption of an animal activity (OPRR Reports; January 12, 1994). If the IACUC places an ongoing project "on hold" or requires a "temporary cessation," these actions are synonymous with suspension, and are reportable. The IO is therefore proposing to compound the seriousness of the incident by placing the institution in violation of prompt reporting requirements of the PHS Policy (IV, F, 3) and the implied requirements of the USDA Regulations [2.31, (d), (6 and 7)]. It is through reporting, with full explanation of circumstances and corrective actions taken, that institutions remain in compliance in spite of identified serious deficiencies.

The IO is correct that he has the authority to take corrective action, in consultation with the IACUC, on suspensions. He may not, however, usurp the IACUC’s authority to suspend an activity, nor may he block a prompt report to OPRR or USDA once initiated by the IACUC.

Corrective actions should include attention to the required involvement of the Attending Veterinarian in planning procedures that may involve pain and distress, adherence to applicable training requirements, and prevention of the issuance of animals to investigators without approved protocols. Even when the applicability of PHS Policy or USDA Regulations is uncertain, the respective agencies recommend that institutions report incidents of this nature. Initial contact could be by telephone. There are many benefits and few disadvantages to doing so. OPRR and USDA view the self-reporting of appropriate institutional oversight actions in a positive light. Others are likely to report this incident by making a formal complaint or allegation (an anonymous caller initially reported the incident to the university hotline). If so, the federal agency would be in a position to quickly confirm that the institution is addressing its problems in compliance with the PHS Policy and USDA Regulations.

A less desirable outcome would be for OPRR or USDA to have to initiate an investigation to gain the necessary information, especially if either agency discovers reporting irregularities. From a public relations standpoint, the adoption of uniform standards for all animal activities, regardless of funding source, is a positive declaration that the institution does not apply a double standard to the care of its animals.

Nelson L. Garnett, DVM
Director, Division of Animal Welfare
Office for Protection from Research Risks
National Institutes of Health

W. Ron DeHaven, DVM
Acting Deputy Administrator,
Animal CareAnimal Plant Health Inspection Service
US Department of Agriculture

Certain Protocol Review columns address problems that can potentially lead to differing interpretations of applicable federal laws, regulations, or policies. As a service to our readers, Drs. W. Ron DeHaven (USDA/APHIS/Animal Care) and Nelson Garnett (NIH/OPRR) graciously provide the interpretation and policies of their respective federal agencies. Readers and column respondents who disagree with these interpretations are encouraged to voice their opinions through Letters to the Editor.