shadow_tr

May the IACUC administratively extend approval of a project that has expired?      
No.  IACUCs do not have authority to administratively extend approval beyond three years.  When IACUC approval expires the protocol lacks valid approval.   Continuation of animal activities in the absence of valid approval is a serious and reportable violation of PHS Policy (see NOT-OD-05-034).

May the IACUC grant conditional or provisional approval?      
The PHS Policy recognizes that the IACUC may approve, require modifications, or withhold approval.  If the IACUC determines that a protocol is approvable, contingent on receipt of a very specific administrative modification or clarification (e.g., a contact telephone number), the Committee may handle the issue as an administrative detail that an individual (e.g., IACUC Chair or Administrator) may verify.  Requests for substantive modifications should result in the protocol coming back to the Committee.  Protocols that lack substantive information necessary for the IACUC to make a judgment (e.g., justification for withholding analgesics in a painful procedure) should be considered incomplete and the IACUC should defer review until the investigator provides the requisite information. Applying descriptors, such as conditional, provisional or interim, when referring to IACUC approval is unclear, confusing, and should be avoided.       

May the investigator begin animal work before receiving IACUC approval?      
No.

What criteria should the IACUC consider when reviewing protocols?      
IACUCs must confirm that:          
* The protocol is consistent with the Guide Link to Non-U.S. Government Site unless a scientific justification for a departure is presented and is acceptable to the IACUC;          
* The protocol conforms to the institution's Assurance;          
* The protocol will be conducted in accordance with the USDA Animal Welfare Regulations if applicable; and          
* The protocol meets the requirements of the PHS Policy at IV.C.1.a.-g.      

For further guidance, the IACUC should refer to the U.S. Government Principles.

Should the IACUC consider the three "Rs" of alternatives when reviewing protocols? (Refinements to research, Reduction of animal numbers, and Replacement with non-animal models)      
The federal mandate in U.S. Government Principle IV to avoid or minimize discomfort, distress, and pain in experimental animals consistent with sound scientific practices, is synonymous with a requirement to implement refinements (e.g., less invasive procedures or use of analgesia).  Similarly, the mandate in U.S. Government Principle III to use the minimum number of animals necessary to obtain valid results is synonymous with a requirement to reduce animal numbers.  U.S. Government Principle III further states that mathematical models, computer simulation, and in vitro biological systems should be considered, and is synonymous with a requirement to replace non-animal models wherever possible.  Thus, consideration of the three "Rs" should be incorporated into IACUC review, as well as other aspects of the institution's program (e.g., investigator training).       

What is considered a significant change to a project that would require IACUC review?      
Examples of changes considered to be significant include, but are not limited to, changes:          
* In the objectives of a study          
* From non survival to survival surgery;          
* Resulting in greater discomfort or in a greater degree of invasiveness;          
* In the species or in approximate number of animals used;          
* In Principal Investigator;          
* in anesthetic agent(s) or the use or withholding of analgesics;          
* In the method of euthanasia; and          
* in the duration, frequency, or number of procedures performed on an animal. [A4, A7]      

Changes in personnel other than the Principal Investigator need not be considered significant provided that an appropriate administrative review mechanism is in place 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. See NIH Guide for Grants and Contracts NOT OD-03-046. The IACUC has some discretion to define what it considers a significant change, or to establish a mechanism for determining significance on a case-by-case basis. Because significant changes require IACUC approval (using one of the valid methods described in question 3 under Protocol Review, and using the criteria described in question 6 under Protocol Review) it is critical that the IACUC clearly define and communicate to investigators its policy and mechanism for determining significance.

Is the IACUC required to review the grant application?      
PHS Policy and the NIH Grants Policy Statement (Part II, Terms and Conditions) require the institution to verify, before award, that the IACUC has reviewed and approved those components of grant applications and contract proposals related to the care and use of animals. This is not an explicit requirement for the IACUC to do a side-by-side comparison of an application/proposal and the IACUC protocol. However, institutions are responsible for ensuring that the information the IACUC reviews and approves is congruent with what is in the application/proposal. Institutions are free to devise a workable mechanism to accomplish this end. One method to prevent inconsistencies between the information submitted to PHS and that on the IACUC protocol is to implement a procedure for direct comparison. Some institutions have delegated this responsibility to a particular office or position (e.g., sponsored programs or compliance office); others ask departmental chairs to verify consistency.      

May the IACUC approve pilot studies?      
Yes.  Pilot studies may be appropriate to determine the technical feasibility of larger studies or to make initial assessments of the effect of procedures on animals (Guide Link to Non-U.S. Government Site - , page 10).  Whether proposed by investigators or required by the IACUC, pilot studies require review and approval by the IACUC in accordance with the PHS Policy.

Is the IACUC responsible for judging the scientific merit of proposals?      
Peer review of the scientific and technical merit of an application is considered the purview of the NIH Scientific Review Groups (SRGs), which are composed of scientific experts from the extramural research community in a particular area of expertise. However, SRGs also have authority to raise specific animal welfare concerns that can require resolution prior to a grant award.      

Although not intended to conduct peer review of research proposals, the IACUC is expected to include consideration of the U.S. Government Principles in its review of protocols. Principle II calls for an evaluation of the relevance of a procedure to human or animal health, the advancement of knowledge, or the good of society. Other PHS Policy review criteria refer to sound research design, rationale for involving animals, and scientifically valuable research. Presumably a study that could not meet these basic criteria is inherently unnecessary and wasteful and, therefore, not justifiable.      

The primary focus of the SRG is scientific merit and the primary focus of the IACUC is animal welfare. The two bodies have differing constitutions, mandates and functions. However, since it is not entirely possibly to separate scientific value from animal welfare some overlap is inevitable. SRGs may raise concerns about animal welfare and IACUCs may question the scientific rationale or necessity for a procedure.

If an animal activity will be performed outside of the US (either by a foreign grantee or by a foreign institution as a subproject for a domestic grantee), is the grantee's IACUC required to review and approve that activity?      
When the grantee is a domestic institution (i.e., domestic grant with a foreign component), PHS animal welfare requirements are applicable.  Accordingly, the grantee remains responsible for animal activity conducted at a foreign site and must provide verification of IACUC approval.  That approval certifies that the activity, as conducted at the foreign performance site, is acceptable to the grantee.  

The grantee IACUC may accept, as its own, the approval of a foreign entity's IACUC; however, the grantee IACUC remains responsible for the review.  Additionally, the foreign entity must complete the "Statement of Compliance with Standards for Humane Care and Use of Laboratory Animals by Foreign Institutions" available from OLAW.  This document certifies that the institution will comply with the applicable laws, regulations, and policies of the jurisdiction in which the research will be conducted, and that the institution will be guided by the International Guiding Principles for Biomedical Research Involving Animals Link to Non-U.S. Government Site.      

If the grantee is a foreign institution then IACUC approval is not required.  The institution completes the Statement of Compliance referenced above.  OLAW encourages foreign institutions to use the standards in the Guide Link to Non-U.S. Government Site, which is available in a number of foreign translations

May standard operating procedures (SOPs) or blanket protocols that cover a number of procedures be utilized in lieu of repeating descriptions of identical procedures in multiple protocols?      
The IACUC must review and approve activities on a project-specific basis, taking into account a number of factors, e.g., the aims of the study, consideration of alternatives, minimization of pain and distress.  For routine aspects of research (e.g., species specific techniques for immunization and titer determinations during antibody production), IACUCs may approve SOPs that can be cited by investigators in their protocols in order to avoid needless repetition.  SOPs should be reviewed by the IACUC at appropriate intervals (at least once every three years) to ensure they are up-to-date and accurate.     

Is IACUC approval required for the collection of samples in foreign countries from captive wild animals or research colonies?      
Collection of biological samples from any live vertebrate animal for the purpose of a PHS-supported activity is covered by the PHS Policy.  If the grantee is a domestic institution, the IACUC should consider the species involved, nature of the specimens, invasiveness of the procedure, risks to personnel, and qualifications of the individual(s) taking the sample(s).      

Grantee institutions should also consult with other agencies of the federal government as appropriate, e.g., US Fish and Wildlife Service, USDA-APHIS-Veterinary Services Link to Non-U.S. Government Site, and the CDC Link to Non-U.S. Government Site, for specimen importation requirements

Is IACUC approval required for the use of animals in breeding programs, as blood donors, as sentinels in disease surveillance programs, or for other non-research purposes?      
Although animals used as sentinels, breeding stock, blood and blood product donors, or for other similar purposes may not be part of specific research protocols, their use is part of the institutional research program and directly supports research activities.  Consequently, the IACUC should review protocols and SOPs that involve animals for such purposes, initially and at appropriate intervals (at least once every three years). 

What guidelines should IACUCs follow for fishes, amphibians, reptiles, birds, and other nontraditional species used in research?      
PHS Policy is intentionally broad in scope and does not prescribe specifics about the care and use of any species, assigning that task to the IACUC and allowing for professional judgment.  Many of the principles embodied in the Guide Link to Non-U.S. Government Site , can generally be adapted to the care and use of various kinds of nontraditional research animals.  IACUCs may seek the advice of experts when necessary, and refer to scientific-based publications prepared by professional organizations with interest in various species.  Appendix A of the Guide references many such publications.       

Is it acceptable to have different individuals named as PI on the grant application and the IACUC protocol?      
Yes.

Should the IACUC inspect laboratories or other sites where investigators use animals?      
Institutions are responsible for oversight of all animal-related activities regardless of how long or where the activity occurs.   Satellite facilities (defined by PHS Policy as a containment outside a core or centrally managed area in which animals are housed for more than 24 hours) and areas where any form of surgical manipulations (minor, major, survival, non-survival) are performed must be inspected at least once every six months by the IACUC as part of the semiannual evaluation.  Institutions have discretion with regard to how they oversee areas used for routine weighing, dosing, immunization, or imaging, but should monitor such areas on a random or fixed schedule to effectively oversee activities at the institution.  USDA requires semi-annual inspection of "animal study areas" defined as areas where USDA covered animals are housed for more than 12 hours.        

How does the IACUC distinguish between significant and minor deficiencies?      
PHS Policy requires the IACUC to make this distinction in its semiannual reports to the Institutional Official.   A significant deficiency is defined as one which is or may be a threat to the health or safety of animals.   Examples include inoperable HVAC, electrical or watering systems, failure of such systems sufficient to affect critical housing and operational areas, and situations such as natural disasters that cause injury, death, or severe distress to animals.  Significant program deficiencies can result from an institution's failure to fully understand or implement some aspect of its animal care and use program required by the PHS Policy, or failure to function according to commitments made in its Assurance, and may reach the level of reportable noncompliance.  Generally, a minor deficiency refers to a problem for which an immediate solution is not necessary to protect life or prevent distress (e.g., peeling or chipped paint).  Ongoing inattention to a minor deficiency may result in a chronic problem indicative of a programmatic failure and may constitute a significant deficiency.

Tulane University, New Orleans, LA 70118 504-865-5000 website@tulane.edu