To VVC Or Not To VVC? That Is The Question

1. To VVC Or Not To VVC?That Is The Question Pam Broussard, Teri Hills, Chris Mannor, Randy Parsons TTI 2018-group presentation Presented by the #1 Group

2. Goals • Understand the Veterinary Verification and Consultation (VVC) portion of the OLAW/USDA Guidance on Significant Changes • Appreciate the benefits of the OLAW/USDA Guidance on Significant Changes for the IACUC

3. Objectives • Distinguish significant changes to eligible approved protocols using DMR/FCR or VVC • Identify policies that must be in place prior to implementing a VVC process at an institution • Outline the benefits of a VVC process

4. Pre-Guidance Significant Changes to Approved Protocols FCR and DMR process for changes:  • from non-survival to survival surgery • resulting in greater pain, distress, or degree of invasiveness • in housing and or use of animals in a location that is not part of the animal program overseen by the IACUC • in species • in study objectives • in Principal Investigator (PI) • that impact personnel safety • in anesthesia, analgesia, sedation, or experimental substances • in euthanasia to any method approved in the AVMA Guidelines for the Euthanasia of Animals • in duration, frequency, type, or number of procedures performed on an animal

5. Post-Guidance Significant Changes to Approved Protocols FCR and DMR process for changes:  • from non-survival to survival surgery • resulting in greater pain, distress, or degree of invasiveness • in housing and or use of animals in a location that is not part of the animal program overseen by the IACUC • in species • in study objectives • in Principal Investigator (PI) • that impact personnel safety • in anesthesia, analgesia, sedation, or experimental substances • in euthanasia to any method approved in the AVMA Guidelines for the Euthanasia of Animals • in duration, frequency, type, or number of procedures performed on an animal* H, I and J now become the VVC

6. Case Study Activity • Take a minute to read and discuss your assigned case study • Discuss if your case study is a significant change and if it qualifies for VVC and why (3 minutes) • Present to the group (4 minutes)

7. Example Case Study A PI is conducting a PHS-funded study examining the aerodynamic changes that occur when the American Dipper (Cinclusmexicanus) transitions from air flight to “flying” in a fluid environment. His protocol involves filming the flight pattern and wing configurational changes in a wind tunnel versus a water flume. The PI submits an amendment seeking to add the implantation of bio-signaling sensors in the wing musculature of his captive American Dippers.

8. Example Case Study Answers Is this a significant change? Yes Is this significant change eligible for the VVC process? No Why? This amendment would not be eligible for the VVC process as it involves a change in the degree of invasiveness, pain, or distress

9. Case Study Activity • Take 5 minutes to read and discuss your assigned case study • Discuss if your case study is a significant change and if it qualifies for VVC and why (3 minutes) • Present to the group (4 minutes)

10. Scenario 2 (PHS-funded) A prominent Flu researcher is examining the ability of various proprietary adjuvants and immunostimulants to increase the protective effect of the annual flu vaccine. During the course of his study he noted that the strain of mouse-adapted flu virus he is using is having unexpected neurotropic (neuroinvasive) effects. His protocol states he will be anesthetizing the mice with isoflurane for the final blood draw (terminal exsanguination) followed by cervical dislocation. The researcher submits an amendment to include the collection of the brain after euthanasia. He also wishes to prevent any confounding effects of the isoflurane on the hippocampus. Therefore, he would also like to change his anesthetic plan to a ketamine/xylazine combination for the terminal blood draw followed by cervical dislocation.

11. Scenario 3 (PHS-funded) A PI is examining the genetic changes associated with thermodynamics and oxygen consumption within and across Deer Mice species (Peromyscusmaniculatus, P. leucopus, and P. aztecus) adapted to varying altitude and temperature ranges. The PI is utilizing mice obtained from the Peromyscus Genetic Stock Center (University of South Carolina). Her breeding colony production has been in significant decline. She submits an amendment to travel to Colorado and trap Deer Mice from various habitat locales.

12. Scenario 4 (PHS-funded) A neuroscientist is studying traumatic brain injury (TBI) and blood-borne biomarkers of concussion in rats. He proposes to anesthetize the rats with Isoflurane, trephine the skull, and place a trans-skull cannula. The cannula is attached to a water-percussion anvil with IV tubing and a precise, measurable percussion force applied to the brain. The cannula is then capped and the rat recovered from anesthesia. Serial blood samples are then taken over the course of two weeks. During the course of the study, the PI finds that the rats are adept at disrupting the cannula placement during the post-surgical survival period. The PI submits an amendment to allow the rats to recover from anesthesia and the percussive event and then 2 hours later re-anesthetize the rats, remove the cannula and close the skull and skin. His reasoning for the 2 hour delay and second surgery is that immediately after the percussive event the rats are prone to acute death and a prolonged anesthesia to remove the cannula may be detrimental to the rats’ recovery.

13. Item Required to Implement the VVC Process An IACUC approved policy that allows the use of the VVC process

14. BUT IF YOU THINK YOU ARE COOL ENOUGH…add the approved items/policies as needed… IACUC reviewed and approved drug formulary IACUC reviewed and approved euthanasia methods approved in the AVMA Guidelines for the Euthanasia of Animals An IACUC policy regarding changes in duration, frequency, type or number of procedures performed on an animal

15. Formative assessment #2 Case scenarios for policy implementation: Example: Your institution does not have a VVC process in place. The IACUC would like to use the VVC process to only approve significant changes encompassing changes in euthanasia methods and drug formularies. Stations with these policies: • An IACUC approved policy that allows the use of the VVC process • IACUC reviewed and approved drug formulary • IACUC reviewed and approved euthanasia methods outlined in the AVMA Guidelines for the Euthanasia of Animals • An IACUC policy regarding changes in duration, frequency, type or number of procedures performed on an animal Place post it notes on the stations that your institution will need before they can use a VVC process

16. Think-Pair-Share Activity Think about the topic for 30 seconds Pair with your neighbor and discuss the topic Share with your table and record your answers on the flip charts Share with the group

17. Topic Think about the processes of DMR/FCR. What are some of the burdens of these processes? Could VVC decrease these burdens?

18. Summative Assessment • T or F for the following: May be approved with the VVC process F A change in PI F A PI wishes to change a non-survival surgery to a survival surgery T An amendment is submitted to change the euthanasia procedures from pentobarbital to CO2 F A flu researcher wishes to change humane endpoints T A PI wishes to add another blood collection time point

19. Summative Assessment Cont. • Check the IACUC approved policies/procedures which would be required to implement the VVC process • Approved anesthesia/analgesia or drug formulary • Policies for changing animal housing locations • Policies for receiving new arrivals • Approved euthanasia guidelines • Policy for approved procedures (duration, frequency, type or number of procedures)

20. Summative Assessment Cont. • What are the benefits of implementing the VVC program? Circle all that apply: • Decrease the regulatory burden on the IACUC • Decrease the number of times changes get submitted • Decrease the administrative burden on the PI • Decrease the time for specific significant changes to be approved

21. Goals • Understand the Veterinary Verification and Consultation (VVC) portion of the OLAW/USDA Guidance on Significant Changes • Appreciate the benefits of the OLAW/USDA Guidance on Significant Changes for the IACUC IACUC Members Will Be Able To: • Distinguish significant changes using DMR/FCR or VVC to eligible approved protocols • Identify policies that must be in place prior to implementing a VVC process at an institution • Outline the benefits of a VVC process