Comments for: Proposed Guidance Regarding Significant Changes to Ongoing Animal Activities

For more information, see NIH Guide Notice (NOT-OD-14-063).

Comment Period: March 11, 2014 - May 15, 2014

 

Name of Organization City and State Comment: Attachments
Institute For Biosecurity, Saint Louis University Saint Louis, MO The last thing IACUC members need are more emails coming their way for non-essential items (and sometimes items that fall outside the current definition of significant changes should be communicated, but this should be a judgement call, not written into regulation). I would even argue that this will be counter-productive because items that really require attention will get lost in the fray.  
University of Connecticut Health Center Farmington, CT I believe that this proposed guidance undermines the professionalism of the IACUC staff. Many of us have advanced degrees, have our CPIA registration from PRIMR, and have many years of experience. I believe we all genuinely care about the animals and want to ensure their well-being. However, this micro-managment from OLAW saddens me professionally; it is as if my professional judgment and experience mean nothing! I truly hope that OLAW re-considers this extra burden that has no additional benefit to the health and well-being of the animals. I can guarantee OLAW that my IACUC does not want to be notified of grammar and typographical errors!  
The Ohio State University Columbus, OH These changes would serve to enhance the regulatory burden and further reduce the effort/funds available for actual animal care. It is difficult to understand how changing the location of an injection site from cephalic to saphenous or switching from minocycline to tetracycline could be a significant impact on animal welfare. professional judgement of the IACUC members and the AV should be the ones determining what is significant at their institution within the current regulatory requirements.  
Virginia Commonwealth University Richmond "The Virginia Commonwealth University IACUC feels that the guidance regarding significant changes under proposed section 'A' be limited to the first bullet ("that have the potential to increase the level of pain or distress of the animal and includes all changes that involve anesthesia, analgesia, sedation, or euthanasia;"). Specifically, we are concerned that guidance proposed in the second bullet ("in frequency, interval, type, number, or anatomical location of: procedures; and substances delivered to the animal.") is too broad and reaches beyond the performance standard approach mentioned in the 8th edition of The Guide. All other guidance suggested in NOT-OD-14-063 is appropriate."  
University of Texas at Austin Austin, Texas 78712 I am writing on behalf of the University of Texas at Austin IACUC committee, of which I am chair. The committee regards new requirements to report minor changes as creating greater burdens on the committee and its staff.  
Federation of American Societies for Experimental Biology Bethesda, Maryland Please see attached response. OLAW RFI Response 05092014.pdf
Duke University Durham, NC We have principal investigators with protocols initially approved for use of 40 mice and others initially approved for the use of 30,000 mice. If the proposed guidance is adopted, addition of 5 mice to the first protocol would be considered a significant change that requires IACUC member notification before approval, whereas up to 3000 mice could be added to the second protocol without triggering IACUC member pre-notification . This does NOT make sense. Classifying addition of over "X" animals as a significant change makes more sense, rather than a percentage of what was previously approved. But even that may be problematic, since the sizes of studies vary considerably between different institutions. OLAW could make a suggestion of where it feels the "line" between a minor and significant addition of animals should fall, but the final decision be left to each individual IACUC, which can make the best decision for their particular institution. It makes sense that changes that could affect animal welfare should not simply be approved by administrative staff. However, there is a middle ground. Some changes can reasonably be approved by IACUC leadership (or other specified IACUC members) with appropriate veterinary input, without requiring prior notification of the entire IACUC. Information about the change could then be provided to the IACUC after the change has been approved. Some examples are changes from one approved method of euthanasia to another or change of commonly used injectible anesthetic or analgesic (e.g. due to non-availability of the approved drug), administration of drug via a catheter rather than direct venous injection, or adjusting the dose of a drug when a range was not originally approved. Forcing these changes to go to the full IACUC before approval slows down the time to approval. This will unduly interfere with research and may lead to increased non-compliance. Our institution has considerable experience using a method of "IACUC Leadership Review" for all non-significant changes (classified as "minor changes" and "minor changes with veterinary review"). Such amendments receive MORE scrutiny than they would if classified as a minor amendment as defined above, since they are initially reviewed by administrative staff and then forwarded to IACUC leadership (after review by a veterinarian if classified as minor with vet review). IACUC members are informed of all changes approved using this method at each IACUC meeting. During the last 5 years, no rank-and-file IACUC members have ever called for review of any changes approved by IACUC Leadership Review. The IACUC Chair did bring two amendments to the full IACUC after approval and the IACUC confirmed approval of the amendment without modification.  
MIT Cambridge, MA Regarding "C. Changes that are not significant may be handled by the IACUC staff without IACUC review and approval. However, the IACUC is to be informed of changes handled by the IACUC staff. This information may be provided after the change has been reviewed and initiated. Such minor changes include but are not limited to: " In my opinion, it is unnecessary and burdensome to require these approved minor changed to be reported to IACUC. The IACUC staff are completely capable of making these decisions and should have the trust of IACUC.  
Columbia University New York, NY It seems as though this proposal would in no way reduce burden on institutions and acutally will do just the opposite, since all minor changes will have to be tracked and reported to the IACUC. It would greatly increase the workload of IACUC staff members, in particular at large institutions with hundreds of protocols. The motivation for this proposal is not clear.  
    At our institution there is already an approved administrative review mechanism in place. Administrative reviews are documented. Copious details of administrative review provided to the IACUC isn't going to improve animal welfare or the overall quality of an animal care and use program.  
Cornell University Ithaca, NY The attached letter is a response to the National Institutes of Health's (NIH's) solicitation of comments concerning the Proposed Guidance Regarding Significant Changes to Ongoing Animal Activities published in the NIH Guide for Grants and Contracts on March 11, 2014, NOT-OD-14-063. Cornell University Comments to NIH on Proposed Guidance to Ongoing Animal Activities .pdf
Animal Welfare Institute Washington, D.C. 1. "The IACUC has the authority to approve ranges of variables as long as it can determine that the range does not interfere with the welfare of the animal AND the range is scientifically justified": As currently written (with OR), this statement allows scientific justification to trump animal welfare. Animal welfare and scientific justification must always be considered concurrently, to ensure one doesn't interfere with the other. 2. "It is the responsibility of the IACUC to clearly define and communicate to investigators its policy for determining significance.": This policy should be stated in all Assurance statements. 3. Part A: Significant changes...not limited to changes": ADD: in stock, strain, or genotypic modification which have known or anticipated effects on animal health and welfare. 4. Part B: Other significant changes: Point 2: Should read: To house or use animals in a location that is not part of the animal program overseen by the IACUC, for the uses approved in the protocol. 5. Part C: Minor changes: Point 1: Should clarify that the total increase does not exceed 10% of the total INITIAL number reviewed and approved by the IACUC.  
    The proposed policy looks fine, but I would like to offer some general comments regarding IACUC approval of changes to studies. In a drug development environment, study conditions change very rapidly. In order to minimize pain or distress to animals while still achieving study goals, it can be very important to allow changes in the study design to capture data on unexpected test article effects. IACUCs are not typically able to respond quickly to these needs and often do not have the knowledge to even determine what changes are appropriate. As an industry, I believe that more authority should be given to veterinarians to manage certain changes that have the ultimate goal of minimizing pain or distress to animals, with follow-up communication to the IACUC. I know that theoretically a very broad range of study procedures can be requested by an investigator and approved by the IACUC to meet this need, but in practice, many inspectors or site visitors are highly critical of this type of system and expect very detailed protocols. I believe that future versions of the Guide should recognize that there could be different ways for institutions to achieve animal welfare goalsthat does not include IACUC review of individual study protocols or changes to on-going activities. This is a system that was valuabe when animal welfare regulations were first promulgated, but does not meet current needs in a drug discovery and development environment, and does not add value to an institution that manages animal welfare through all of its policies and procedures and does not depend solely on an IACUC approved document. IACUCs still serve an important role in establishing institutional policies and providing oversight, but are not the only way, and are one of the least efficient ways, of managing the operational details of study conduct within a research institution. However as the industry has evolved, it has led to higher expectations for direct IACUC control rather than for it to serve an oversight function, which I suspect was the original intent.  
Pennington Biomedical Research Center Baton Rouge, LA This IACUC appreciates OLAW's efforts to clarify for awardee institutions what is considered a significant change to an ongoing animal activity that requires IACUC review. We recognize that the intent of the guidance is to ensure the careful IACUC consideration of animal welfare when protocol modifications are proposed. We also recognize the difficulty in providing guidance that adequately addresses the myriad of experimental scenarios that any research setting may encounter. However, unless we are misinterpreting it, the guidance provided by the combination of bullet point #2 under section A and bullet point #2 under section C is so broad that it removes much if not all of the IACUC's ability for "determining significance on a case-by-case basis." For example, if an IACUC in its institution's protocol modification policy provided as guidance for investigators that a change in route of administration, for example a change from intravenous to subcutaneous administration, is less invasive or would create less pain or distress; under this new guidance and the criterion outlined by these 2 bullet points this change must be considered significant. We think that every IACUC could give numerous day-to-day examples of experimental scenarios that are of equal or lesser invasiveness that fit under bullet point #2 of section A and when combined with bullet point #2 under section C leads to inflexibility in the guidance creating undue burden on the investigator and the IACUC while not improving animal welfare. This IACUC would request that the language of these points be reconsidered to allow for less invasive experimental procedures to generally be considered non-significant.  
MUSC Charleston, SC   OLAW comments.pdf
    The requirement to report all minor changes to the committee substantially trivializes the oversight nature of the committee, and negates the importance and professionalism of support staff. The IACUC is charged with the focusing on the humane care and treatment of the animals, and this proposed guidance completely takes away from that. The added value of most of these proposals (such as contact information updates, correction of typographical errors & grammar) is EXTREMELY small compared to the administrative burden it would put on the committee. The IACUC should not have to deal with or worry about changes that are so insiginficant and have nothing to do with the health and safety of the animals.  
UTHealth Houston, TX Please clarify the following language in Part C. "However, the IACUC is to be informed of changes handled by the IACUC staff. This information may be provided after the change has been reviewed and initiated" How much information is required to be provided to the IACUC? is a list of protocols that have had administratively reviewed change requests approved sufficient? or must the details of each change be reported to the committee as a whole? If all of this information is available in an electronic system that all IACUC members have access too, does that count as notification? Or must a separate communication be sent to each member?  
University of South Florida Tampa Florida Unfortunately all such "guidance" as the effect of codifying into regulations, however much that may not be the intent. The IACUC should be able to delegate to staff, IACUC chair or such other appropriate person all such oversight responsibilities as it feels appropriate. For example, there is likely no one other than the DVM on the committee that has any ability to evaluate a change in anesthetic. The PI is however the most likely person to have both the knowledge and the ability to determine the appropriateness of the change from a scientific point of view. There should be greater flexibility for the PI using such phrases such as "Analgesia provided for first 24 hours by agents such as --, with responses appropriately observed and recorded." There is much too much reliance on the (often absent) knowledge base of the IACUC members and far too little based on the knowledge base of the PI. As long as a record is made the IACUC is free to comment observe and seek consultation if it detects a welfare issue. 99% of such changes have no animal welfare implications whatsoever. IACUC review should be needed if there is a SIGNIFICANT potential for a negative impact on animal welfare. (rarely the case in the list of proposed item "guidance".)  
University of Arkansas for Medical Sciences Little Rock, AR In my opinion, the requirement to report all minor changes to the committee substantially trivializes the oversight nature of the committee, and negates the importance and professionalism of support staff  
UConn Health Center Farmington, CT The requirements proposed in C. where the IACUC is to be informed of changes to protocols that are not significant, and executed by IACUC staff, is administratively burdensome. It is also not clear how institution of such a change would improve animal welfare or enhance the quality of PHS-supported activities. Thus, C. should be eliminated for consideration by OLAW.  
University of Washington Seattle, WA On Using Too Few Animals If animal numbers are based on a power analysis for a null hypothesis test, the PI is required to use all animals that were planned for the test, or else the test is statistically invalid. Stopping early increases the type I error level (false discovery), because nobody ever stops early if the result is promising but not significant. So, a reduction in animal numbers in group sizes for a planned experiment that will use a null hypothesis test is not something a PI should be doing from a purely statistical point of view (unless using a sequential stopping rule (SSR) to control type I error rate). However, from an ethical point of view it may be best to stop an experiment early even if it breaks the rules of pure statistics. If an effect is much larger than expected, the obtained p value may be so small that it is a virtual certainty that the experiment could be replicated (the size of the obtained p value does contain information about how likely an experiment is to be significant in an identical replication). Using up the rest of the animals in that situation just to satisfy the pure statistical mandate is unethical because it wastes the animals. This is built into the SSR, but few investigators use it yet. Many, and in some cases most, of the animals on our protocols are not used in experiments, but they must be approved on the protocol. Animals used as breeders, animals that are euthanized because of their genotype or gender, are all approved on the protocol. These are known to be estimates and should not be taken as quotas that must be achieved or else the protocol is noncompliant. What is the PI of a fishing protocol to do if a smaller than expected number of fish comes up in the trawl? An IACUC should approve a maximum number of animals to be used on a protocol. The IACUC can help investigators to use statistics appropriately (every IACUC should include a person with a solid background in elementary statistics). The IACUC should not try to micromanage the ultimate sample size and number of animals used on an experiment by experiment basis as the research is actually conducted. The PI assumes responsibility for determining these things, and reviewers of journal manuscripts ensure that sample sizes and replications are believable. Ethics and Animal Numbers final.pdf
University of Florida Gainesville, FL IACUC focus is the health and welfare of the animal. At our University we have over 1200 active protocols, which requires significant effort of the committee. The requirement to report all minor changes to the committee such as those described in section C that are handled by the staff without IACUC review and approval, only trivializes the nature of the committee. This also negates the importance and the professionalism of the IACUC staff. How about a little common sense here!  
Office of Animal Welfare, University of Washington Seattle We have some questions of clarification before we comment. Please respond to the email listed above. Thank you! 1. Section A: Does "Direct Impact" include both negative and positive impact(s)? 2. Section A, second bullet point: Could you provide a definition/clarification of "type" for both procedures and substances? 3. Under Section B: Does a change in animal numbers include increasing and decreasing numbers? 4. What is the official definition of a "Minor Change"?  
VA Puget Sound Health Care system Seattle, Washington I appreciate OLAW attempt to clarify what constitutes a significant change in animal use on IACUC protoocls. However, I think the policy needs some revision. I think each IACUC should be able to use judgement to decide what constitutes a significant change. Some of these proposed rules take away that ability from the IACUC and will create more burden for the IACUC and investigators. In point A I think it should only be considered a significant change if there is an increase in frequency, interval, type, number of procedures, not a decrease, AND the procedures would result in a significant increase in discomfort or invasiveness. Some procedures are not invasive at all, such as weighing animals on a study, so even an increase might not be considered significant. In addition if an investigator wants to decrease the number or frequency of procedures, and this may positively impact animal welfare, why is that a significant change? Perhaps the statement should be reworded to say that changes are significant if the IACUC determines that the change may have a significant negative impact on animal welfare. In part C, while I agree that the IACUC should be informed about minor changes in animal use, it seems overly burdonsome and irrelevant to require the IACUC to be notified about corrections in grammar, typographical errors and contact information, or changes to animal housing location if that location is part of the animal use program and is a regular housing room.  
    Our institition already has an approved administrative review mechanism in place. Administrative reviews are maintained and documented in the system. A list of administrative review provided to the IACUC isn't going to improve animal welfare or the overall quality of an animal care and use program. Our committee is very busy and would not benefit from a long list of administrative changes.  
    Please the attached document for comments. Thank you. Response to OLAW NOT-OD-14-063.pdf
NIH Intramural Research Program Bethesda, Maryland The NIH Intramural Research Program appreciates the opportunity to comment on this proposed change in guidance. Our comments are included in the attached PDF document: NIH IRP Response to Proposed Guidance Regarding Signf Chgs-Final_5-14-2014. NIH IRP NIH IRP Response to Proposed Guidance Regarding Signf Chgs-Final_5-14-2014 .pdf
    While I understand that the intent of this guidance is to clarify what constitutes significant and minor changes, the overall effect will be to increase administrative burden on the IACUC staff, members and researchers. This is going to be a particularly onerous proposition for those of us without electronic protocol/management systems. As an example, It's not currently required that the IACUC be notified of changes in housing location if they are within the managed facilities. We leave management of in-facility space to the animal facilities staff so they have full leeway to adjust housing as needed, and have no reason to track this from the IACUC side. Changes in minor issues like typographical and grammatical errors are currently handled administratively and there is no benefit to be realized by adding them to the already extensive list of DMR activities the IACUC reviews. This also applies to some of the other minor changes listed. The net result is going to be more paperwork and follow-up required for minor issues that only need minimal handling currently.  
    In my experience, the IACUC regulations don't reach the people who actually do the animal work. Other than my own lab, I have not met a single student, post-doc, or sub-I that really abides by the regulations or the protocol. There is no repeat training. There is no way to even get the correct sedatives and analgesics to abide by protocols. Investigators have hundreds of mice and do not know about it.  
Tufts University Boston, MA I think that the significant changes listed in A may be unintentionally too stringent given the way they are currently stated. Specifically: "In frequency, interval, type, number, or anatomical location of: procedures; and substances delivered to the animal." For instance as written this would categorize the following changes as significant: Subcutaneous injection given in the hip area vs. between the shoulders Blood draw taken from an alternate site (saphenous vein vs cephalic vein) Adding additional sedation for a stressful procedure Under the current wording the examples above would fall under significant, however I believe these could be appropriately handled by IACUC staff/designated review.  
  East Lansing, MI Although the stated Purpose of NOT-OD-14-063 is to reduce the burden, NOT-OD-14-063 actually increases the burden to IACUCs and their staff without any demonstrable benefit to the animals. Requiring the staff to report to the IACUC the items listed in Item C of NOT-OD-14-063 has no demonstrable benefit to the animals but does increase the workload of the staff and the Committee if OLAW expects the IACUC to review such a report. In my personal opinion, the greatest impact of NOT-OD-14-063 on the regulated community is the message it sends to IACUCs and their staff. NOT-OD-14-063 does not give due consideration to the intelligence, education, training, and experience of IACUC members and their staff nor to their genuine concern for the animals for which they are responsible. Presenting a list of items to be considered effectively removes the opportunity for IACUCs to use their collective wisdom and experience (professional judgment and performance standards) to do what is best for the animals. That, coupled with the directive to the IACUC to concern itself with clerical issues, suggests engineering standards. I am saddened by the lack of appreciation of the commitment and effort put forth by the hard working men and women who staff or serve on animal care committees.  
Univ of Texas at Austin Austin, TX In 2003, OLAW published guidance (NOT-OD-03-046) that allowed IACUCs to consider a change in protocol personnel as a modification that could be handled administratively, provided that an appropriate review mechanism was in place to adequately verify training, experience, occupational health program enrollment, etc. This was done in recognition of the fact that requiring the addition of personnel to be handled as a significant change had the potential to add unnecessary burden and prolonged delays to the process without providing any benefit in regards to humane care and use protections. As an experienced laboratory animal veterinarian, I wish to point out that a very similar situation exists when changes in anesthetic or analgesic methods and/or dosages are indicted. It is not uncommon to find that the perioperative drug regimen initially chosen when the protocol was written and approved does not perform optimally when the study is actually conducted. If the drugs/dosages listed in the approved protocol do not perform adequately, it benefits both the research project and the well-being of the research animals to make appropriate adjustments to the methods used. However, as was the case for personnel changes, this is a situation where strict adherence to the requirements for approval of a significant change can seriously impede the ability of an institution to approve and implement these humane refinements in a timely fashion. I suggest that OLAW use this as an opportunity to provide IACUCs with the flexibility to consider changes in the drugs and or doses used for anesthesia, analgesia, sedation, or euthanasia as an administrative change if an appropriate review process is in place to assure that the revised regimen has been determined to be safe and efficacious in the species and context proposed. As per the 2011 Guide, it is a responsibility of the Attending Veterinarian to ensure appropriate methods are used for immobilization, sedation, analgesia, anesthesia, and euthanasia and also to provide guidance and oversight regarding surgery and perioperative care, so it follows that each IACUC should incorporate veterinary review as part of the process put in place to approve this type of protocol modification. It should be noted that in the vast majority of cases, changes such as this are currently routed through a designated member review process and reviewed solely by a veterinarian. Allowing this veterinary review to be routed administratively in these situations will streamline the process without materially affecting the actual review process. Of course, if OLAW feels that the policy and guidance currently in place allows some flexibility and latitude in how changes in drugs and dosages may be rapidly addressed when animal welfare is impacted, then I suggest that this be explained as part of your response to this comment. This would be a very valuable interpretation for local IACUCs.  
    The following items should not be required to be reported to the IACUC when handled as minor changes by the IACUC staff: - "change in stock, strain, or genetic modification, unless the new stock, strain, or modification results in abnormalities that require special support" - "change to house or use animals in a location that is currently used for the same purpose and is part of the animal program overseen by the IACUC" - "change in personnel other than the Principal Investigator" - "correction of typographical errors" - "correction of grammar" - "contact information updates" The IACUC should be aware of and agree upon the types of changes that are handled administratively by the IACUC staff, however a requirement to report each and every one of these types of changes to the IACUC is unnecessary and unduly burdensome.  
LAVCS San Diego, CA Section A. - "..that have the potential to increase the level of pain or distress of the animal AND includes all changes that involve anesthesia, analgesia, sedation, or euthanasia"; Is this an "and" statement? Would it apply to changes limited ONLY to anesthesia, analgesia, sedation, or euthanasia? For example, if the procedure(s) and pain category do not change and the veterinarian approves a change to the anesthetic, sedative or analgesic regimen to provide better pain relief, would this still be a major modification? What about a change in euthanasia method that is still compliant with current AVMA guidelines? - "in frequency, interval, type, number, or anatomical location of: o procedures; and o substances delivered to the animal". - Would this include a change such as from IP to SC (or vice versa) in rodents? Section C: Would changes of correction of typographical errors, or grammar; and/or contact information updates mean there is going to be a new type of approval allowed? Would protocols requiring these types of administrative changes be considered Approved? Modifications Required (In) to Secure Approval or something else? Comments to Proposed Guidance Regarding Significant Changes to Ongoing Animal Activities.pdf
U of Iowa Iowa City, IA The following items should not be required to be reported to the IACUC when handled as minor changes by the IACUC staff: "change in stock, strain, or genetic modification" - There currently exists no requirement for the IACUC to review the details of each stock, strain, or genetically modified animal to be used and so changes in same should not have to be reported to the IACUC each time they occur "unless the new stock, strain, or modification results in abnormalities that require special support". A change from Duroc to Landrace swine, Balb/C to FVB mice are examples of insignificant changes that not only don't need to be reported to the IACUC when handled as minor changes by IACUC staff, but aren't even required to be reported to the IACUC by the principal investigator in the first place. "change to house or use animals in a location that is currently used for the same purpose and is part of the animal program overseen by the IACUC" - There currently exists no requirement for the IACUC to review the details of changes in housing location that are part of the centralized animal housing program. Transfers of animals from approved centralized managed housing location A to approved centralized managed housing location B are not required to be submitted to, or reviewed by, the IACUC. These are insignificant changes that not only don't need to be reported to the IACUC when handled as minor changes by IACUC staff, but aren't even required to be reported to the IACUC by the principal investigator or the animal facility manager in the first place. "change in personnel other than the Principal Investigator" - As indicated in the guidance, changes in personnel must have an appropriate administrative review "conducted to ensure that all such personnel are appropriately identified, adequately trained and qualified, enrolled in applicable occupational health and safety programs, and meet other criteria as required by the IACUC." However, as long as that process is in place, there is no value in requiring the reporting of all such administratively approved personnel changes to the IACUC. The added value compared to the associated administrative burden would be infinitely small. "correction of typographical errors" - The added value compared to the associated administrative burden would be infinitely small. "correction of grammar" - The added value compared to the associated administrative burden would be infinitely small. "contact information updates" - The added value compared to the associated administrative burden would be infinitely small. Each of the above items adds unnecessary administrative burden and provides no real value to the IACUC. Additionally these reports would waste time of IACUC members spent reviewing unnecessary data.  
Albert Einstein College of Medicine BRONX, NY Although the stated Purpose of NOT-OD-14-063 is to reduce the burden, NOT-OD-14-063 actually increases the burden to IACUCs and their staff without any demonstrable benefit to the animals. Requiring the staff to report to the IACUC the items listed in Item C of NOT-OD-14-063 has no demonstrable benefit to the animals but does increase the workload of the staff and the Committee if OLAW expects the IACUC to review such a report. In my personal opinion, the greatest impact of NOT-OD-14-063 on the regulated community is the message it sends to IACUCs and their staff. NOT-OD-14-063 does not give due consideration to the intelligence, education, training, and experience of IACUC members and their staff nor to their genuine concern for the animals for which they are responsible. Presenting a list of items to be considered effectively removes the opportunity for IACUCs to use their collective wisdom and experience (professional judgment and performance standards) to do what is best for the animals. That, coupled with the directive to the IACUC to concern itself with clerical issues, suggests engineering standards. I am saddened by the lack of appreciation of the commitment and effort put forth by the hard working men and women who staff or serve on animal care committees.  
Howard University College of Medicine Washington, DC 20059 Section B, bullet 1 and Section C bullet 1 are somewhat confusing. Section C, bullet 2 could benefit from some examples. Section C, bullet 3: Changes in genetic modification may not always be 'not significant;.  
Biogen Idec Cambridge, MA This guidance is for the most part very clear and reasonable. However, requiring the IACUC to be notified of every typographical or grammatical correction or update to contact information--corrections which have no bearing on the protocol objectives or activities, nor on animal care or welfare--would be an onerous burden upon the IACUC staff, and also needlessly flood IACUC members' email inboxes. IACUC staff should be permitted to freely make such changes behind-the-scenes, with no requirement to update the IACUC.  
The American Association of Immunologists Bethesda, Maryland (See also attached letter) The American Association of Immunologists (AAI), the largest professional association of immunologists in the world, appreciates having this opportunity to submit comments on the National Institutes of Health (NIH) "Proposed Guidance Regarding Significant Changes to Ongoing Animal Activities" (NOT-OD-14-063) ("Proposed Guidance"). AAI represents more than 7,800 of the world's leading research scientists and physicians who are dedicated to understanding the immune system through basic research, resulting in improved means to prevent, treat, and cure disease. Largely through funding from NIH, our members are working on some of the most critically important and promising areas of biomedical research, including: - developing effective vaccines for influenza, HIV/AIDS, and agents of bioterrorism; - discovering new defenses against re-emerging tuberculosis and drug-resistant bacterial infections; - regulating debilitating autoimmune diseases such as diabetes and rheumatoid arthritis; - developing treatments to prevent rejection of transplanted organs and bone marrow; and - developing novel immune-based therapies for cancer. As you know, immunology research often utilizes laboratory animals. AAI members strongly support efforts to ensure the humane use of animals in research and take their responsibilities in this regard very seriously. AAI is very concerned, therefore, that the Proposed Guidance will actually increase regulatory burden on research scientists and reduce the ability of investigators and Institutional Animal Care and Use Committees (IACUCs) to exercise professional judgment and utilize performance-based standards, all without benefiting the animal subjects or the outcome of the research. As a founding member of The Federation of American Societies for Experimental Biology (FASEB), which is comprised of 26 scientific societies collectively representing over 115,000 biomedical researchers, AAI would like to endorse the comments submitted by FASEB on May 9, 2014. In particular, we endorse the notion that the Proposed Guidance is unnecessary. Further, we endorse the FASEB-recommended modifications, should OLAW decide to go forward with the Proposed Guidance, including clarifying that the definition of "significant change" should exclude a reduction in 1) the number of animals, and 2) the frequency or number of procedures administered to an animal; and removing the requirement that the entire IACUC must be informed of non-significant changes. We appreciate having this opportunity to comment. Comments on OLAW RFI on Significant Change to Animal Activities.May 12 2014.pdf
    Reporting all minor changes is an unnecessary burden that takes time away from the important goal of ensuring animal welfare. IACUC staff should not waste time reporting and IACUC members should not waste time reading or hearing about such changes.  
University of Washington Seattle, WA The personnel that rely on the guidelines set forth in the PHS Policy on Humane Care and Use of Animals appreciate OLAW's effort to reduce the administrative burden on both the institutions and the researchers. Based on the proposed guidance it is not clear to us how this will be accomplished. We are submitting these questions for clarification of the proposed guidance and its efforts. 1. Regarding significant changes, giving IACUCs discretion to determine their own policies for determining significance would seem to be inconsistent with the prescriptions for determining significant changes laid out in A and B. Further, A and B raise a number of questions about proper interpretation as written. a. We are seeking clarity on how 'direct impact' in Section A would be defined. Does this include items that would result in an improvement in animal welfare? For example, if an investigator was able to do a fewer number of blood draws to achieve their endpoints would this require a significant change as defined in A - change in frequency of a procedure? b. In Section B regarding the change in animal numbers. We assume that this would be both an increase and a decrease in animal numbers as written. A decrease in the number of animals required to reach a scientific objective has not typically been tracked in protocol review - particularly in the preparation portion of the study when a significant change would be submitted for approval. This is usually something that would be captured in the annual updates or on 3 year renewals in the section regarding previous experience on the protocol and incorporation of the 3 R's. This has the risk of increasing administrative burden and has the potential to put individuals who use fewer animals in a non-compliant situation. 2. Regarding section C we feel that it would be adding additional administrative burden to the staff that support the IACUC and the members of the IACUC to have them review the information that is outlined in this section. Although we agree that it would be beneficial for the IACUC to be informed of the first 5 items listed there does not seem to be any potential benefit to the animal welfare of informing the IACUC of the final 3 items mentioned - typographical errors, grammar corrections or contact information updates. Thank you again for your efforts to reduce administrative burden and give the community an opportunity to comment on the proposed guidance.  
The University of Texas at San Antonio San Antonio, Texas The requirement to report all minor changes (room changes?, adding personnel?, adding a small number of animals that is less than the threshold agreed to in our PHS Assurance?, adding a funding source?) to the committee substantially trivializes the oversight nature of the committee, unnecessarily increases their workload, and negates the knowledge, professionalism, and competence of support staff!." The IACUC focus is the on the health and welfare of the animals and they should not be distracted from that to review minor administrative actions taken by the IACUC staff, especially when our approved PHS Assurance agrees that those minor administrative actions may be reviewed and approved by the professional IACUC staff. Don't become the 'regulatory creep' we all hear about and do NOT want to be!  
ACUP Consulting Memphis, TN Although the stated Purpose of NOT-OD-14-063 is to reduce the burden, NOT-OD-14-063 actually INCREASES the burden to IACUCs and their staff without any apparent benefit to the animals. I think the greatest impact of NOT-OD-14-063 on the regulated community is the message it sends to IACUCs and their staff. NOT-OD-14-063 does not give due consideration to the intelligence, education, training, and experience of IACUC members and their staff nor to their genuine concern for the animals for which they are responsible. Providing a list of items to be considered effectively disregards the professional judgment, years of experience, collective wisdom and performance standards (which OLAW's mandated document- the Guide stresses is of utmost importance) of the IACUC and staff. That, coupled with the directive to the IACUC to concern itself with clerical issues, suggests engineering standards. There is no proposed benefit for the animals by this additional administrative burden, which I thought was the IACUC's main charge. I am saddened by the lack of appreciation of the commitment and effort put forth by the hard working men and women who staff or serve on animal care committees.  
Office of the Chief Veterinary Medical Officer, Office of R&D, Dept of Veterans Affairs Atlanta, GA   2014 05 14 Comment on proposed OLAW guidance NOT-OD-14-063.pdf
University of Maryland College Park Our IACUC allows a number of these changes (via a written policy approved in FC) to specifically be done by either AR or DMR but we still include them on every meeting agenda and the committee has access to the list post-approval as this language indicates. It appears that this model would still be appropriate were the language used here be put in place. However, I'm reluctant to add another layer to an already incredibly slow process. If this clarification is absolutely necessary and I do not believe it is, then I would prefer that OLAW delineate that inclusion in the minutes and/or other committee documentation meets the standard of "informed of changes" which is too vague for daily use. The other item of clarification needed is what information needs to be included in "informed of changes", is a list of amended protocols sufficient or does that "informed" part need to include the exact details of each change (ie. PI Bob changed his mice from DBA to Swiss Webster)?  
Duke University Durham, NC - There is concern regarding setting a numerical limit for considering a significant increase in non-USDA covered species. Approved IACUC animal numbers can represent a large range of animal numbers (20 - 20,000 mice, rats, fish, etc.). Setting a 10% limit indicates that an increase in 2 animals may be significant for one protocol; however, an increase in 1,999 may not be significant for another protocol. When looking at it as the welfare impact on an individual animal, I believe setting an absolute number to constitute significant vs. minor change only aides in improving human welfare by having a clearly defined line-in-the-sand. Allowing individual IACUCs to choose the line is more appropriate for their individual situations is more suitable. I do not believe the percentage should be the focus, more attention should be placed on the scientific justification for individual animal use. - There currently exists no requirement for the IACUC to review the details of each stock, strain, or genetically modified animal to be used unless there is a phenotypic characteristic that may affect the animal welfare. If an investigator chooses to use mice, the use of any wild-type strain or approved vendor of mice should be covered in that approval (unless specifically indicated otherwise in the protocol to meet experimental goals or desired/anticipated phenotypic states). An amendment should not be required to change from one wild-type mouse to another. In addition, if mice/rats are bred in house for a specific period of time, they essentially become a new sub-strain. This strict requirement to have every stock, strain, or GEM animal approved in the protocol would lead to a significant amount of unavoidable non-compliance.  
Council on Governmental Relations & Association of American Universities Washington DC The Council on Governmental Relations (COGR) is an association of 190 research universities and affiliated academic medical centers and research institutes. The Association of American Universities (AAU) represents 60 leading public and private U.S. research institutions. We recognize and understand the delineation of significant changes as outlined in Sections A and B of the proposed guidance. These sections are consistent, as noted, with guidance offered in response to Frequently Asked Questions (FAQs) in 1995, as modified concerning personnel in 2003. It is equally important to acknowledge that the PHS Policy affords the Institutional Animal Care and Use Committee (IACUC) the discretion to determine the meaning of significance in all cases and the changes outlined in Sections A and B are to be used as a guide in making that determination. The PHS Policy does not define significance and OLAW cannot use the mechanism of guidance to establish new policy requirements. In line with the Office of Management and Budget (OMB) 2007 Final Bulletin for Agency Good Guidance Practices, we interpret Sections A and B as offering OLAW's current thinking on the meaning of significant changes and acknowledge the advice of establishing a mechanism that determines significance and communicating that mechanism to our investigators. One of the principal goals of the OMB Bulletin was to ensure that guidance documents do not impose new legally binding requirements. Thus, this OLAW Guidance should not set a requirement but, rather, offer useful advice and counsel to grantees. We object, however, to Section C concerning changes that are not significant and we strongly recommend the elimination of Section C. If the changes are not significant, they do not require action on the part of the IACUC. Such changes do not need to be reported to the IACUC, a "requirement" that exceeds the PHS Policy. There is no regulatory requirement for the IACUC to consider the stock, strain, or genetic modifications in animals used in research. There is no regulatory requirement for the IACUC to consider changes in the housing of animals currently approved for the activity within facilities overseen by the IACUC. As previous guidance noted, there is no requirement for the IACUC to review changes in personnel other than the principal investigator. And it would be entirely unnecessary and a burden with absolutely no benefit to notify the IACUC of corrections of typographical or grammatical errors or changes in contact information. In issuing guidance on the meaning of significance changes in on-going animal activities, we urge OLAW to make clear the purpose of the guidance - to offer its current thinking on the topic - and to address the specific issue in the guidance - the meaning of significant changes as described in Sections A and B - and to eliminate Section C from the guidance document. Anthony P. DeCrappeo, COGR Hunter R. Rawlings, AAU COGR AAU on OLAW Guidance May 2014.pdf
American Physiological Society Bethesda, MD See attached letter. APS Final ltr to OLAW on substantial change RFI.pdf
    I appreciate the revised guidance and the intent to "reduce the burden on investigators and institutions by facilitating greater autonomy within local IACUCs". However, tracking and reporting modifications to protocols that the IACUC has determined NOT to require DMR or FCR review by the IACUC is, in fact, incredibly burdensome and this proposed requirement warrants further consideration. This requirement represents a substantial waste of resources for all parties involved, including the IACUC staff and the personnel who serve on the IACUC.  
UConn Health Farmington, CT Having corrections to typographical errors, corrections of grammar and contact information updates go the IACUC over stresses the IACUC office for little benefit. As an IACUC member and reviewer, this information can be dealt with within the IACUC administration with confidence that it will be efficient, accurate and legal. The purpose of such detailed oversight is hard to understand.  
  Fort Collins CO This guidance document appears to be a means to establish new policy requirements, as such it states "the IACUC has discretion to add to the following section A. and B." While this guidance gives IACUCs the opportunity to add to the OLAW guidance it limits an IACUC's ability to deviate from the guidance. Depending on an institution's organization of their animal care program the items OLAW defines as significant in section A and B, may in fact not be significant, which could also be handled by administrative review should an institution's IACUC establish those procedures, and reduce the regulatory burden of the institution. For example, if there is a change in personnel and the co-investigator on the protocol is to become the PI on the protocol, that does not necessarily need to be considered a significant change requiring full IACUC review and approval. A change in the route of administration of a substance does not necessarily need to be reviewed by the IACUC. This could be handled administratively by the Attending Veterinarian based on an institutions IACUC policy. This guidance seems to narrow the guidance previously provided and I urge OLAW to continue to allow the IACUC to determine what is significant and the processes to handle those changes in animal use. OLAW should be cautious about adopting guidance into a policy.  
University of Illinois Urbana, IL Defining "all changes that involve anesthesia, analgesia, sedation, or euthanasia" as significant may not be appropriate for many institutions. Changes between approved agents and methods consistent with IACUC-approved guidelines should not be considered significant, allowing them to be handled administratively. In view of institutional diversity as well as autonomy, an IACUC must establish its own process for allowing administrative approval of non-significant changes. Limiting approval to "IACUC staff," as proposed in Section C, is inconsistent with this stated purpose. The IACUC being informed of minor changes, routinely handled administratively, is not a current PHS Policy requirement. Notification of these minor changes on an on-going basis will create burdens for administrative staff as well as for committee members. References to IACUC notification in Section C. should be deleted. In addition, implying that IACUC notification is needed for typographical or grammatical errors is excessive. Predicting exact needs several years ahead often is problematic. OLAW's proposed guidance suggests a 10% change in the number of animals not regulated by USDA is not considered significant. The PHS Policy (IV.D.1.a) specifies that applications and proposals identify the "approximate number of animals to be used." Restricting approval for increased animal numbers to significant changes creates additional administrative burden.  
University of Illinois, Urbana-Champaign Champaign, IL I strongly object to the portion of the proposed guidance, "However, the IACUC is to be informed of changes handled by the IACUC staff. This information may be provided after the change has been reviewed and initiated." I believe this addition would pose an undue and unnecessary burden on the IACUC review system. As a current member of the IACUC at the University of Illinois, I have intimate knowledge of the process, and of the time and effort needed to maintain compliance and to conduct adequate review of animal research. Minor changes in protocols have already been acknowledged as not needing IACUC review by OLAW. As a committee member, I have no interest in being informed of such minor changes. Presenting this information to me constantly, which would happen at large institutions where minor changes like this happen numerous times a day, would serve only to trivialize the IACUC's position as an oversight body. As an IACUC member, I always have complete access to protocols and all changes are documented and available should a I need to know of them. This language should be removed from the proposed guidance.  
Big 10 Conference universities numerous cities and states Please see attached file. NOT-OD-14-063 response.pdf
University of Connecticut Health Center Farmington, CT I appreciate the effort of OLAW regarding its guidance in the ongoing animal activities. It will be best served by giving the institution and IACUC regarding the Section A. Because with board certified lab animal veterinarian in the committee and institution have implemented the ranges for analgesia, anesthesia, so any change in those ranges doesn't require DMR and FCR. Section C - Remove all last three bulleted points - Correction of typographical errors, grammar and contact information updates. Thank you.  
University of Missouri Columbia, MO   Response to OLAW RFI Significant Changes 5-2014.pdf
No affiliation, Private citizen.   When I first read the proposed guidance I was asked for an opinion. My response was, "No big deal, this guidance furthers our understanding of OLAW expectations and matches procedures our IACUC already has in place. I think it is a good thing." Then I read both NABR's and ACLAM's comments on the proposed OLAW guidance in question and I was amazed at the diversity between my opinion and their comments. Needless to say, I do not agree with either organization's comments. As an animal advocate and former IACUC member, I believe OLAW's Proposed Guidance on Significant Changes serves to further our understanding of best practices that protect the animal research subjects whose use we oversee. I do not see this guidance as burdensome to investigators and believe that if the proposed guidance is changed to accomodate NABR and ACLAM suggestions, the animal research subject will be the loser, not the Principal Investigator or the human being who will benefit from the research. While IACUC's should be allowed autonomy, in my experience, IACUC's need assistance in developing policies, procedures, and positions. Otherwise, there is often pressure from their administration, from PIs, and from the need to improve profitability to "give-in" to demands and take the path of least resistance. Having clear and firm guidance provides the IACUC with the regulatory support necessary to protect the animal research subject in the face of overt and/or covert pressure and this is the IACUC's first and foremost duty. While I certainly understand the need to reduce regulatory burden and to help our scientists make needed research discoveries that benefit mankind, I can't dismiss my primary duty as an IACUC member - that of an animal advocate - and therefore, I cannot support the ACLAM and NABR positions on this guidance. Instead, I support OLAW's proposed guidance and see it as necessary and in the best interest of our animal research subjects.  
Oregon Health & Science University Portland, Oregon Our personal professional comments (not necessarily representative of our institution) It is our opinion that OLAW and the IACUC's need to focus on the welfare of animals and not be involved in micromanaging administration of each IACUC program. From the March 10, 2014 report by National Science Foundation on page 13: "What investigators expressed frustration with were requirements that increased their administrative workload but were not perceived to improve the care and treatment of animals. These issues have significant implications for the day-to-day conduct of research and function of IACUCs." (Our comment: IACUC administrative burden is already heavy and we encourage OLAW to reduce administrative burden rather then over-interpret regulations.) "On the topic of guidance, respondents suggested that "should" statements in the Guide are enforced as "must" statements by the NIH Office of Laboratory Animal Welfare (OLAW), which has the effect of imposing new rules rather than offering interpretations." (Our comment: We encourage OLAW to not over-interpret recommendations that are articulated in the Guide for the Care and Use of Laboratory Animals.) "Their concern is that in addition to the requirements in statutes and regulations, new requirements are being created through guidance and FAQs, which is not the intent or purpose of guidance." (Our Comment: We agree with this statement wholeheartedly.) "Federal requirement that all experiments have to be predetermined and that exact animal numbers have to be statistically justified forces researchers to project these quantities years into the future, and then continually file amendments for any deviation." (Our comment: Identifying all changes in animal numbers as significant and requiring IACUC review does not benefit animal welfare and is overly burdensome administratively especially in cases where animal numbers are decreased.) Additional Comments: There currently exists no requirement for the IACUC to review the details of each stock, strain, or genetically modified animal to be used and these should not have to be reported to the IACUC each time they occur unless the new stock, strain, or modification results in abnormalities that require special support. Most changes in strain are insignificant changes that not only don't need to be reported to the IACUC but aren't even required to be reported to the IACUC.  
Michigan State University East Lansing, Michigan Please see attached. NOT-OD-14-063 Response MSU.pdf
American Psychological Association Washington DC   APA Comments on OLAW Guidance_Significant Changes.pdf
The University of Connecticut Health Center Farmington, CT I agree with the guidance except for the last three bullet points. I believe that informing the committee that a typographical error and/or grammar was fixed or that wrong contact information was corrected will result in an unnecessary burden on the IACUC office. What has any of these to do with ensuring the welfare of animals? Our regulations should be helping to ensure welfare of animals, not "office issues".  
  Athens, GA Aside from the fact that almost all IACUCs are meeting the oversight outlined in the RFI by ongoing protocol review, the chance that IACUCs could use this guidance to increase regulatory burden is tremendous. Most notably, IACUC staff could misinterpret this guidance to start developing special reporting mechanisms for changes that are not significant. It is also troubling to note that missing a stated single value is noncompliant. Does this mean that an investigator states they will collect 50 microliters of blood, but because 2 drops come out (about 100 microliters) they are now noncompliant. There must be some room for procedural variance.  
      Response to NOT-OD-14-063.pdf
    These are common sense guidance statements that should be approved immediately. Consider if there is a way to allow non-invasive observations or sample collections (such as fecal collection, weighing, or similar) with minimal required action, or even as a pilot in between full approval. Also, the bullet that lists anesthesia, analgesics, etc, should be split into 2 seperate bullet points to aviod confusion.  
American College of laboratory Animal Medicine Chester, NH   ACLAM OLAW Response.pdf
National Association for Biomedical Research Washington, DC NABR applauds OLAW's stated purpose for proposing the subject guidance, the dual objectives of supporting the use of performance standards and professional judgment by Institutional Animal Care and Use Committees (IACUC) in following the Public Health Service (PHS) Policy for the Care and Use of Laboratory Animals (Policy) and reducing the burden on investigators and institutions by facilitating greater autonomy within local IACUCs. The recently released National Science Board Report, Reducing Investigators' Administrative Workload for Federally Funded Research, identifies animal research and IACUC requirements as making a significant contribution to administrative burden. The report highlights the requirement for making changes in research protocols as one considered a particular problem by investigators. OLAW is positioned to help remedy the situation with improved guidance on the subject. NABR hopes this opportunity is taken. To accomplish its stated purpose and minimize regulatory burdens, NABR agrees with the proposal's introductory statements about the responsibilities, authority and discretion of IACUCs. However, after emphasizing IACUC autonomy in determining what is a significant change in animal activities as provided in the Policy (IV.B.7), detailed lists of what is and is not significant are provided. This approach undermines the IACUC's performance, negates its professional judgment and defeats the purpose of this OLAW guidance. Given the diversity of PHS grant awardees' laboratory animal programs, it is inherently difficult to list examples that will apply and be understood by all. Some of the proposed guidance as written will be misinterpreted and, therefore, more burdensome on institutions. Further, and of greater concern, some of the listed examples go beyond the current requirements of PHS Policy. In keeping with the Office of Management and Budget publication, Final Bulletin for Agency Good Guidance Practices (January 2007), this proposed guidance is intended to offer OLAW's advice concerning the subject issue, but should not establish additional regulatory requirements. NABR recommends the nature of the document be made clear in the introduction. It is intended as a guide for following the PHS Policy. The reference to "meeting the standards of the PHS Policy" in the statement of purpose is imprecise. The Health Research Extension Act of 1985 authorized the Secretary of Health and Human Services, through the Director of the National Institutes of Health, to establish "guidelines." NABR's specific comments to illustrate the points made above can be read in the attached document. NABR members are anxious to meet their obligations to protect animal welfare in accordance with PHS Policy. In these times of declining financial resources, it will greatly benefit all PHS assured institutions and their laboratory animals, if administrative time and costs are minimized. We appreciate OLAW's assistance in these endeavors. NABR Comments to OLAW 5-15-14.pdf
University of Alabama at Birmingham Birmingham, AL Please see attached file. Comments for Proposed Guidance- Significant Changes 5-15-14.pdf
Tulane University New Orleans, La Many of these changes (B) will add an administrative burden to both the IACUC staff and the committee with no increase in animal health and welfare oversight. I do not think that the IACUC staff should responsible for "approval" of anything. Changes that are made by the IACUC staff should not be designated as a change that needs approval. Typographical errors or grammar should not be considered a change that needs approval not is it something that requires a mechanism to notify the committee. Contact information updates are another aspect that is handled by the IACUC staff and has no bearing on the research nor is there any reason for the committee to be notified of these changes. Change to house or use animals in a location that is currently used for the same purpose and is part of the animal program overseen by the IACUC also does not need 'approval" or notification to the committee. Areas that new to the program or areas where the use changes to a survival surgery are inspected by the IACUC prior to work being conducted and thus do no fall under this designation. Change in personnel other than the Principal Investigator - We currently have an appropriate review process to ensure that personnel are appropriately identified, adequately trained and qualified, enrolled in applicable occupational health and safety programs, and meet other criteria as required by the IACUC." However, as long as that process is in place, there is no value in requiring the reporting of all such administratively approved personnel changes to the IACUC. OLAW will need to delineate what they consider appropriate mechanism for documentation that meets the standard of "informed of changes".  
University of Texas System Austin, TX The University of Texas System provides its comments in the attached document Comment on Proposed Guidance Regarding Significant Changes.pdf
    The primary purpose of the IACUC is to oversee the humane care and use of animals. Most IACUC committee members are unpaid and most IACUC Office staff are overworked. The requirement to report minor and/or administrative changes to the committee places undue burden on members and staff, and does not substantially contribute to animal health or wellbeing. Furthermore, it reduces the amount of time IACUC members have to spend reviewing protocols and amendments. In addition, adding this type of busy work provides a disincentive for individuals to serve on the IACUC. If oversight is necessary, require IACUCs to have a defined procedure for handling minor and/or administrative changes and add this item to the OLAW Checklist to be included in the semi-annual programmatic review.  
    see attached NIH comments regarding signficant changes.pdf
University of Illinois Urbana, IL I object to the portion of the proposed guidance, "However, the IACUC is to be informed of changes handled by the IACUC staff. This information may be provided after the change has been reviewed and initiated." I believe this addition would pose an undue and unnecessary burden on the IACUC review system. As a professional IACUC administrator, I have intimate knowledge of the process, and of the time and effort needed to maintain compliance and to conduct adequate review of animal research. Minor changes in protocols have already been acknowledged as not needing IACUC review by OLAW. Committee members would have no interest in being informed of such minor changes, and presenting this information to them constantly (as changes such as these are made numerous times daily in a large institution) would serve only to trivialize their position as an oversight body. IACUC members always have complete access to protocols, and all changes are documented and available should a committee member need to know of a change. This language should be removed from the proposed guidance.  
University of Florida Gainesville, Fl I think this would be a burden on IACUC staff and committee members. Members get enough notifications about various issues already. I don't think they will be interested in being informed about personnel changes, typographical errors, contact information updates, etc or any of the information under C. That would serve no purpose to burden them with such information and might cause them to not pay attention to a real important notification. The IACUC staff would have to compile all of this information and figure out a way to inform the committee. I don't see anything wrong with the way things are presently being addressed.  
    I support OLAW's efforts to reduce regulatory burden while preserving animal welfare. Further reductions in unnecessary regulatory burden are sorely needed to allow more focus on animal welfare. Currently we spend an inordinate amount of time checking boxes which does nothing to improve animal welfare.  
University of Minnesota Minneapolis, MN My personal professional comments (not necessarily representative of my institution) are inserted following the relevant verbiage in the notice. The following items should not be required to be reported to the IACUC when handled as minor changes by the IACUC staff: "change in stock, strain, or genetic modification" - There currently exists no requirement for the IACUC to review the details of each stock, strain, or genetically modified animal to be used and so changes in same should not have to be reported to the IACUC each time they occur "unless the new stock, strain, or modification results in abnormalities that require special support". A change from Duroc to Landrace swine, Balb/C to FVB mice, domestic short hair to long hair cat, rhesus to cynomolgus primate, etc. are all examples of insignificant changes that not only don't need to be reported to the IACUC when handled as minor changes by IACUC staff, but aren't even required to be reported to the IACUC by the principal investigator in the first place. "change to house or use animals in a location that is currently used for the same purpose and is part of the animal program overseen by the IACUC" - There currently exists no requirement for the IACUC to review the details of changes in housing location that are part of the centralized animal housing program. Transfers of animals from approved centralized managed housing location A to approved centralized managed housing location B are not required to be submitted to, or reviewed by, the IACUC. These are insignificant changes that not only don't need to be reported to the IACUC when handled as minor changes by IACUC staff, but aren't even required to be reported to the IACUC by the principal investigator or the animal facility manager in the first place. "change in personnel other than the Principal Investigator" - As indicated in the guidance, changes in personnel must have an appropriate administrative review "conducted to ensure that all such personnel are appropriately identified, adequately trained and qualified, enrolled in applicable occupational health and safety programs, and meet other criteria as required by the IACUC." However, as long as that process is in place, there is no value in requiring the reporting of all such administratively approved personnel changes to the IACUC. The added value compared to the associated administrative burden would be infinitely small. "correction of typographical errors" - The added value compared to the associated administrative burden would be infinitely small. "correction of grammar" - The added value compared to the associated administrative burden would be infinitely small. "contact information updates" - The added value compared to the associated administrative burden would be infinitely small.  
University of Illinois at Urbana-Champaign Urbana, IL This is not required by law and will only trivialize the important roles that the IACUC plays, evaluating significant changes to protocols. It will result in hundreds of emails clogging the inbox of IACUC members, and there is no reason that they should be informed of minor administrative changes in protocols.  
University of Florida Gainesville, Florida I do not think administrative changes such as change to house or use animals in a location that is currently used for the same purpose and is part of the animal program overseen by the IACUC, locations inspected during the semi-annual inspection; change in personnel other than the Principal Investigator ; correction of typographical errors; correction of grammar; and contact information updates need to be brought before the IACUC. We make hundreds of personnel changes, dozens of room reassignments and grammar or contact updates in a month. The IACUC is not really interested in these administrative changes nor should they be. These changes do not effect animal welfare.  
University of Mississippi University, MS - that have the potential to increase the level of pain or distress of the animal and includes all changes that involve anesthesia, analgesia, sedation, or euthanasia; - See more at: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-063.html#sthash.SJmVDTqW.dpuf A comment on the above significant change: We have a relatively small animal research population at our campus. As the AV, I read every protocol and if it goes to DR, I am always one of the reviewers. Also, based on the regulations, our protocol requires the investigator to consult with me if using anesthetics, analgesics, and/or performing surgery or other painful procedures. Few if any members of our IACUC are very familiar with anesthetics and analgesics used in many of the species used here. Therefore, when there is a request for modifying the anesthetic/analgesic regimen in an approved protocol, the committee almost always defers judgement to me for the appropriateness of it. We currently process these as significant amendments, but would it be possible to let me (the AV) determine the approval without the amendment/request going through the IACUC?  
Radford University Radford, Virginia "The IACUC has the authority to approve ranges of variables" needs to be clarified. What is a "range of variables"? I think I understand but wouldn't want to be mistaken, resulting in inadvertent non-compliance. "It is the responsibility of the IACUC to clearly define and communicate to investigators its policy for determining significance." Examples need to be provided here rather than being discussed as a clarification in an upcoming issue of Lab Animal that many of us don't have time to read anymore. For instance, is it acceptable to provide in the agenda, and thus the minutes, of the next meeting as is commonly done in IRB? Can they be passively posted in a known location of the IACUC's secure website or does it need to be an active distribution? Or?  
SRI International Menlo Park, CA   SRI Comment to OLAW guidance on significant changes.pdf
Massachusetts General Hospital Boston, MA 02114 Enclosed please find the signed comment letter on behalf of Massachusetts General Hospital from Dr. Harry W. Orf, Senior Vice President for Research. MGH Comment Ltr 5.2014.pdf


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