Patricia Brown

A word from OLAW and USDA.

It is my opinion that Eagle’s work as described with privately owned dogs is a clinical study that has been reviewed by and is being overseen by the Clinical Trials Committee of Great Eastern University’s veterinary school. Therefore, it would not fall under the auspices of Great Eastern’s IACUC. The dogs are privately owned and do not belong to either Eagle or Great Eastern. In addition, the owners have given informed consent, which should have included the possibility of anesthetic complications and fully described what is meant by ‘periodic’ fMRI studies. If the work was a clinical study that was designed for research purposes only, then an approved IACUC protocol and oversight would be necessary. The imaging and anesthesia would have to be fully described, and Southedge Hospital would need to be cited as a satellite location and inspected by the IACUC. T h e f r u s t r a t i on o f t h e s ch o o l ’s veterinarians is understandable, as Eagle’s attitude appears to be rather dismissive of their concerns. However, as a veterinary neurologist, Eagle is well within his rights to utilize the information gleaned from these diagnostic tests in his research.

A word from OLAW.

acquire the same scientific information”1. In this scenario, the reviewer’s suggestion to prioritize reduction before welfare would reduce the number of animals used in Foxworthy’s experiment, but it would also increase the pain and distress for each of those animals, probably beyond an acceptable threshold. The Office of Laboratory Animal Welfare endorses prioritizing the welfare of individual animals above the principle of reduction, prescribing that “procedures with animals will avoid or minimize discomfort, distress, and pain to the animals, consistent with sound research design”2. Foxworthy’s preference, using more animals so that each animal experiences less pain, is a better option than the alternative, using fewer animals with each animal experiencing more pain. Foxworthy’s design will maximize the welfare of each rat in his experiment and reduce the presence of unwanted variables in the resultant dataset. Every IACUC is charged with evaluating the experimental models and design proposed in each protocol. They must consider what level of pain and distress is acceptable for each animal and what methods are most likely to generate reliable data. IACUC members should recognize that experimental groups are made up of individual animals, and it is the IACUC’s responsibility to help ensure the welfare of each and every animal used for research at the institution. Principal investigators must strive to generate high quality data while concurrently minimizing the pain and distress of their research animals. In this scenario, Foxworthy should be allowed to perform his research as described in his protocol with group sizes large enough to minimize pain and distress for each animal.

A Word from APHIS and OLAW

In response to the issues posed in this scenario, the US Department of Agriculture Animal Plant Health Inspection Service (USDA-APHIS) and the National Institutes of Health Office of Laboratory Animal Welfare (NIH-OLAW) provide the following clarifications: In this scenario, the Institutional Animal Care and Use Committee (IACUC) is reconsidering its standard operating procedure for who can be a Principal Investigator (PI) on an IACUC protocol. Great Eastern’s SOP allows a postdoctoral scholar (postdoc) to function as PI if the faculty mentor is listed on the protocol as the sponsor. The Animal Welfare Act Regulations (AWAR) requires all persons involved in animal use to be qualified to perform their duties and designates the research facility as being responsible for providing training and instruction1. The PI is defined as “an employee of a research facility, or other person associated with a research facility, responsible for a proposal to conduct research and for the design and implementation of research involving animals.2” The regulations also outline the responsibilities of the PI which include but are not limited to: consulting the Attending Veterinarian on painful/distressful procedures, considering alternatives to painful/distressful procedures, and providing the appropriate medications for procedures causing more than momentary or slight pain/distress unless withholding is scientifically justified in writing2,3. As a result, it is the responsibility of the IACUC to determine whether persons designated as the PI using an AWA regulated species meet the definition and fulfill the qualifications and responsibilities as set forth by the regulations. The Public Health Service Policy does not contain specific guidance on who can serve as PI for research involving animals. The Policy at IV.C.1.f states that “the IACUC shall determine that personnel conducting procedures on the species being studied will be appropriately qualified and trained in those procedures.4” The Policy also states that “no PHS support for an activity involving animals will be provided to an individual unless that individual is affiliated with or sponsored by an institution which can and does assume responsibility for compliance with the Policy, unless the individual makes other arrangements with the PHS.4” The flexibility provided by the Policy allows the institution to define the PI within the constraints that it finds acceptable. This differs from the NIH definition of the PI on a grant application: “the individual judged by the applicant organization to have the appropriate level of authority and responsibility to direct the project or program supported by the grant5,6”. In some cases, postdocs may be the PI on an NIH award, especially with its current interest in supporting early stage investigators7. Such postdocs qualify in their own right to serve as PIs using Great Eastern’s definition and should list themselves as their own faculty mentor. It is also of note that OLAW allows the individual listed as the PI on the grant to be different from the PI on the IACUC protocol8. ❐

Tough decisions about protocol review

on during protocol review, research suggests that IACUCs might not be fulfilling this federally mandated responsibility according to the intent of the regulations and the PHS Policy. Table 2, from a recent study, lists the top seven topics most frequently discussed and four of the five topics least frequently discussed during protocol review5. The total number of times that each topic was mentioned was subdivided to indicate the role of the IACUC member that initiated the discussion on that topic6. For the five most frequently discussed topics, different IACUC members mentioned them in nearly the same rank order, suggesting that the “essence” of the committee was thinking alike, despite the varying constituencies they represent, i.e., scientist, veterinarian, non-affiliated, etc. Similarly, for the four topics discussed the fewest number of times, the rank order was similar between IACUC members representing different constituencies. The topics that were most often addressed during the protocol review were related to statistics, study design, selection of the appropriate anesthetic, and appropriate monitoring interval. Such issues are easier to objectively evaluate and quantify, and, thus, more likely to require revision prior to approval. The tougher issues for the IACUC to address are those that are more subjective and less easily quantified. Addressing these relies on multiple perspectives and on engagement of the collective essence of the committee. Such issues include the societal value/benefit of the studies, knowledge advancement, species choice rationale, and alternatives to using live animals as research subjects. These topics were discussed least often. As a result, there is a lower likelihood that the investigator will be required by the IACUC to clarify or expand on these topics, and the IACUCs may run the risk of missing critical information that could impact their decisions regarding the proposed activity. Tough decisions about protocol review

Response to Protocol Review Scenario: A Word from OLAW and the USDA

Both the PHS Policy and the Animal Welfare Act and Regulations indicate that an IACUC may conduct protocol reviews by either FCR or by DMR1,2. In this charge, each IACUC member shall be provided with a list of proMoreover, the IACUC is tasked with overseeing the institution’s animal program, and if any member has a concern, they should discuss it with the committee. In the future, the Great Eastern University IACUC should consider adopting a written policy that clearly delineates which members can request FCR. They should also find a method whereby voting members who are unavailable for the 72 hour review are identified, so that alternate members can act in an official IACUC member capacity allowing them to request FCR.

Response to Protocol Review Scenario: A word from USDA and OLAW.

vate practice on privately owned pets, and since the pets will not be housed at Great Eastern University or handled by university personnel, the institutional collaboration policy would cover this research. A memorandum of understanding should be drafted between the private practice veterinarians and Great Eastern University outlining the responsibilities of all parties, particularly in relation to establishing requirements for notifying pet owners or obtaining their consent, approving humane methods of removing ticks from the dogs, and upholding appropriate practices of acquiring and handling ticks with due consideration of occupational health and safety concerns If Montfort’s work triggers the Great Eastern University IACUC’s policy on tissue collection, a simple protocol would suffice, serving to document appropriate practices of acquisition, use and disposal of vertebrate tissue and addressing occupational health and safety issues. This type of protocol would stand as a matter of record and would not require inspection of the premises of private veterinary practices. If the research focuses on the tick itself, then a memorandum of understanding between the collaborating veterinarians and Great Eastern University would provide safeguards for all parties without increasing the administrative burden on the project’s participants. Since all handling will occur off-site by licensed veterinarians is another—outside the scope of this column, but still worth considering to avoid potential legal entanglement in the future. The grants management office may consider legal review by the Great Eastern University team to avoid potential future liability.

A word from USDA and OLAW.

no immediate concern for the welfare of animals in Clark’s current research: the IACUC approved the protocol and any pain and distress is addressed and relieved. The veterinarian, IACUC and PI should work collaboratively and consider taking a few subsequent steps. Firstly, they can carry out one or more pilot studies and evaluate the experimental context of these techniques, such as time from surgery to experimental endpoint or next surgical procedure. Secondly, they can assess the quick, obvious resolution, or it can be more complicated and require upfront investment by the IACUC, as is the case with Clark. With changes of this magnitude, the IACUC should first address appropriateness and, here, the effect such changes could have on research that is funded by an institution like the NIH. Significant changes in methodology should not occur in the middle of a grant; instead, the suggested change should be thoroughly investigated and implemented at an appropriate time. This approach is especially appropriate in While everyone agrees that animal welfare is the most important priority, and while both perspectives are correct, the potential negative cost to the PI’s research and laboratory is daunting. The principles of the 3Rs, as reflected in the Guide for the Care and Use of Laboratory Animals, require that researchers and IACUCs consider the “availability or appropriateness of the use of less-invasive procedures” and “unnecessary duplication of experiments” when reviewing a protocol1. Addressing these principles can be a A word from USDA and OLAW

Response to protocol review scenario: A word from OLAW.

1. National Institutes of Health. Guidance on significant changes to animal activities. Notice NOT-OD-14-126. (National Institutes of Health, Washington, DC, 26 August 2014). must be easily accessible and must welcome such inquiries in order to facilitate reliable, consensus-based team decisions. The intent of the new guidance is to allow researchers to do their work with as little hindrance as possible. The IACUC should develop policies that support this intent without compromising compliance. Articulating conditions (examples are always from the funding agency to move in this new direction. In addition to the evidently flawed policy, we would see these errors as arising from a communication problem: when there is even a glimmer of doubt, staff should consult with others on interpretations of regulations and decision-making. The attending veterinarian and IACUC chair A word from OLAW

Breeding without research. A word from OLAW and USDA.

committee that all of Spencer’s “unforeseen” problems are resolved. Any future protocols the IACUC action. Future work on the animals (frogs) under this protocol should be resumed only after obtaining permission 2. Silverman, J., Suckow, M.A. & Murthy, S. The IACUC Handbook 2nd edn. 158 (CRC Press, boca Raton, FL, 2007). 3. Office of Laboratory Animal Welfare. Institutional Animal Care and Use Committee Guidebook 2nd edn. 97 (US Department of Health and Human Services, Washington, DC, 2002, reprinted 2008).