protocol review Jerald Silverman, DVM, Column Coordinator
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© 2014 Nature America, Inc. All rights reserved.
Accidental failure to administer an analgesic The IACUC, veterinary staff and Office of Research Compliance at Great Eastern University conscientiously tried to assure that all animals received the pain- relieving drugs that were approved by the IACUC. Nevertheless, mistakes did happen occasionally, such as when one lab technician e rroneously believed that another technician was a dministering a once-daily dose of a nalgesic to a dog, with the result that the dog did not receive its pain relief at all. The error was d iscovered the next day and reported to the IACUC. The correct schedule of p roviding analgesia was reinitiated, with the l aboratory manager clarifying work assignments for the t echnicians. An IACUC subcommittee investigated the incident and determined that it was an
Response Missed analgesia Patricia N. Coan, DVM, PhD, DACLAM, Joleen K. Adams, DVM & Dana Glass-Mattie, DVM
We feel that the IACUC administrator was correct: the dog’s category of use should be D. A similar situation a few years ago included clarification from the Office of Laboratory Animal Welfare (OLAW) and USDA verifying that category D would be the correct pain category1. Unfortunately, the procedures done on the animal and the animal’s condition were not presented in this scenario. Nevertheless, the dog did not receive the daily dose of analgesia that should have been provided in accordance with the IACUC-approved protocol. Great Eastern University was correct in forming a subcommittee to evaluate the incident. The Animal Welfare Act and Regulations define a painful procedure as “any p rocedure that would reasonably be expected to cause more than slight or momentary pain or d istress in a human being to which that LAB ANIMAL
nfortunate but unintentional error in a u laboratory that had no previous deviations from its approved protocols. No suspension or other sanction was deemed necessary. At the next IACUC meeting, the s ubcommittee’s report of the episode was discussed, approved and entered into the minutes. The Office of Laboratory Animal Welfare was informed of the incident and its resolution. When it came time to submit the US Department of Agriculture (USDA) annual report, the IACUC administrator placed the dog in column D (pain or d istress a lleviated by drugs). The IACUC chair questioned this placement, b elieving that the dog should be in column E (pain or distress not a lleviated by drugs) because of the prolonged time that had passed before analgesia was once again
provided. But the administrator stated that using column D was in line with a previous c larification from the USDA 1 and, in addition, that column E is reserved for animals for which pain- or distress-alleviating drugs are not used because of experimental needs. In this case there was no experimental need to withhold drugs, which the administrator said supported the use of column D. D o y o u t h i n k t h a t t h e IA C U C administrator’s explanation and actions were correct, or was the IACUC chairman right? Would you have taken any actions that were not taken by the Great Eastern IACUC?
rocedure is applied, that is, pain in excess p of that caused by injections or other minor procedures”2. The animal did not receive its daily dose of analgesia, and hence the veterinary medical care that was provided was i nadequate, in violation of USDA Animal Care Resource Guide Policy #3: Veterinary Care and Policy #11: Painful Procedures3. Policy 3 was v iolated in that adequate post-procedural care was not provided and the animal did not receive its once-daily a nalgesic dose. Policy 11 was violated in that the post-procedural analgesic regimen described in the IACUCapproved protocol was not f ollowed. Policy 11 states that “[a]nimals e xhibiting signs of pain, discomfort, or d istress such as weight loss, decreased appetite, abnormal activity level, adverse r eactions to t ouching inoculated areas, open sores/necrotic skin lesions, a bscesses, lameness, conjunctivitis, corneal edema, and p hotophobia are expected to receive appropriate relief unless written scientific justification is provided in the animal activity proposal and approved by the IACUC”3. The USDA annual report form i ndicates that categor y E should include the
“ number of animals upon which teaching, e xperiments, research, surgery or tests were conducted involving accompanying pain or distress to the animals and for which the use of a ppropriate anesthetic, analgesic or tranquilizing drugs would have adversely affected the procedures, results, or interpretation of the teaching, research, experiments, surgery, or tests.” Thus, we feel that the dog should not be placed in c ategory E, because analgesics were withheld as a result of human error and not for scientific reasons. There are two areas of concern: the lack of adequate veterinary care and training of the technical staff. We would have required the technical staff members to receive additional training to ensure they understand the importance of reading and following the IACUC-approved protocol, documenting all procedures and treatments in the animal’s medical record and notifying the attending veterinarian of any questions or problems.
Volume 43, No. 10 | OCTOBER 2014 347
1. Brown, P. & Gipson, C. A word from OLAW and USDA. Lab Anim. (NY) 38, 347 (2009).
1. Brown, P. & Gipson, C. A word from OLAW and USDA. Lab Anim. (NY) 38, 347 (2009). 2. Animal Welfare Regulations. 9 CFR. Chapter 1 Subchapter A,1.1 Definitions. 3. US Department of Agriculture. Animal Care Policy Manual (USDA, Riverdale, MD, 2014).
protocol review
Coan is the Attending Veterinarian and Director of the Office of Laboratory Animal Care, Adams is a Clinical Veterinarian in the Office of Laboratory Animal Care and Glass-Mattie is the Director of Animal Compliance Support at the University of Tennessee, Knoxville, TN.
Response Law does not address human error
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© 2014 Nature America, Inc. All rights reserved.
Alison D. Pohl, MS, MT, rLATg, CPIA & Ron G. Wallace, PhD, CIH, RBP
In evaluating this scenario, we assume that the analgesia schedule called for more than 1 day of analgesics, meaning that the animal may have experienced a higher degree of pain than anticipated because of the missed dose. But analgesics were given, and so it is appropriate to place the animal in category D on the USDA annual report. There are limitations to the quality of data provided on the annual report. Pain experienced by animals can be c ategorized as no or momentary pain, pain relieved by administration of analgesics or pain not relieved by administration of analgesics because their use would adversely affect the research results. It would be difficult to j ustify the placement of these animals in category E, because analgesics were given, albeit late, and the delay was a result of human error and not an IACUC-approved action. Great Eastern’s IACUC concluded that this was an unfortunate error and no sanctions were considered necessary. This denotes an attitude of acceptance and complacency toward human error. It would be nice if there were no mistakes when using animals for research, testing or training; unfortunately, that is not likely to ever be the case. Its inevitability, however, does not mean that human error should not be addressed. Great Eastern’s IACUC should have required the investigator responsible for the research to submit a plan of action to ensure the appropriate administration of analgesics in the future. This plan could include c onfirmation checks such as checklists, a buddy system or supervisor sign-off to rocedures make sure that all required p are completed. Confirmation is especially important when a m istake could lead to
348 Volume 43, No. 10 | OCTOBER 2014
unnecessary pain or distress to animals, the minimization of which is one of the main focuses of animal welfare in research. The IACUC must find a b alance between t aking the trouble to ensure that procedures are done correctly and living with mistakes. Will the overall results be better if we aim to make no mistakes (but probably make a few istakes anyway) or if we just accept that m are going to happen and pay the price when they do? Each IACUC should determine what an acceptable balance is and how to bring personnel up to the appropriate level of rigor required to strike that balance. It is the IACUC’s responsibility to set the standard. Pohl is IACUC Coordinator and Research Compliance Monitor and Wallace is Biological Safety Officer and IBC Coordinator at UConn Health, Farmington, CT.
Response What’s right? Yolanda P. Villarreal Acosta, BA
The IACUC administrator should have provided an explanation of how the USDA pain and distress categories are assigned. The focus in this scenario is whether the animal’s experience of more than m omentary, pain or distress was relieved (category D) or not relieved ( category E)1. As the IACUC chair expressed, category E is appropriate because the animal experienced pain prior to relief: “Animals must be listed in Column E if they are s ubjected to painful procedures and the anesthetics, analgesics, tranquilizing drugs or other palliative treatment did not adequately preclude more than slight or momentary pain or distress”1. The IACUC Guidebook states, “It is the responsibility of the IACUC to c ritically e valuate all research protocols for the potential to cause pain or distress and assess the steps that are to be taken to enhance animal well-being”2. In this s cenario, the lab technicians took the f ollowing steps: a dminister daily analgesia; realize that a dose was missed; reinitiate analgesia schedule; contact the IACUC. If there were no f urther steps in the approved protocol for the lab technicians to follow, then the IACUC should re-e valuate the protocol
and ask the i nvestigator responsible for the research to discuss with the attending v eterinarian further steps to be taken, such as r ecording details of analgesic administration (technician, time, dose, etc.); monitoring animals more than once per day and d ocumenting this m onitoring; and having the investigator or other d esignated individual confirm that duties are c ompleted. If the d esignated i ndividuals are unable to monitor an animal or provide a scheduled treatment, then arrangements can be made with the veterinary staff to ensure this task is done. The protocol should also include guidance on managing a missed dose and list criteria that warrant intervention by the attending v eterinarian, who should have been immediately contacted along with the IACUC. The IACUC should have also considered re-training the staff members to confirm that the lab technicians and the investigator understand the privilege of working with research animals. The IACUC may require that the investigator submit a follow-up report and that the lab documentation be checked by the IACUC during semi-annual laboratory inspections. Staff members should be reminded that the veterinary staff and IACUC office are available and should feel comfortable contacting either group for assistance at any time. With everyone working together to ensure that research animals receive the proper care, compliance can be maintained while research is carried out responsibly. Finally, the IACUC, upon being notified of the incident, should have phoned OLAW and USDA to alert them of the incident prior to sending the formal report to OLAW. The USDA inspector will evaluate the report d uring the annual inspection of the institution. 1. Office of Animal Care and Use. Guidelines for Preparing USDA Annual Reports and Assigning USDA Pain & Distress Categories (National Institutes of Health, Bethesda, MD, 2013). 2. ARENA/OLAW. Institutional Animal Care and Use Committee Guidebook 2nd edn. (Office of Laboratory Animal Welfare, Bethesda, MD, 2002). Acosta is Research Compliance Coordinator for the IACUC, IBC, CSC & R&LSC in the Office of Research Integrity, Office of the Vice President for Research at the University of Texas at San Antonio.
www.labanimal.com
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© 2014 Nature America, Inc. All rights reserved.
Accidental failure to administer an analgesic The IACUC, veterinary staff and Office of Research Compliance at Great Eastern University conscientiously tried to assure that all animals received the pain- relieving drugs that were approved by the IACUC. Nevertheless, mistakes did happen occasionally, such as when one lab technician e rroneously believed that another technician was a dministering a once-daily dose of a nalgesic to a dog, with the result that the dog did not receive its pain relief at all. The error was d iscovered the next day and reported to the IACUC. The correct schedule of p roviding analgesia was reinitiated, with the l aboratory manager clarifying work assignments for the t echnicians. An IACUC subcommittee investigated the incident and determined that it was an
Response Missed analgesia Patricia N. Coan, DVM, PhD, DACLAM, Joleen K. Adams, DVM & Dana Glass-Mattie, DVM
We feel that the IACUC administrator was correct: the dog’s category of use should be D. A similar situation a few years ago included clarification from the Office of Laboratory Animal Welfare (OLAW) and USDA verifying that category D would be the correct pain category1. Unfortunately, the procedures done on the animal and the animal’s condition were not presented in this scenario. Nevertheless, the dog did not receive the daily dose of analgesia that should have been provided in accordance with the IACUC-approved protocol. Great Eastern University was correct in forming a subcommittee to evaluate the incident. The Animal Welfare Act and Regulations define a painful procedure as “any p rocedure that would reasonably be expected to cause more than slight or momentary pain or d istress in a human being to which that LAB ANIMAL
nfortunate but unintentional error in a u laboratory that had no previous deviations from its approved protocols. No suspension or other sanction was deemed necessary. At the next IACUC meeting, the s ubcommittee’s report of the episode was discussed, approved and entered into the minutes. The Office of Laboratory Animal Welfare was informed of the incident and its resolution. When it came time to submit the US Department of Agriculture (USDA) annual report, the IACUC administrator placed the dog in column D (pain or d istress a lleviated by drugs). The IACUC chair questioned this placement, b elieving that the dog should be in column E (pain or distress not a lleviated by drugs) because of the prolonged time that had passed before analgesia was once again
provided. But the administrator stated that using column D was in line with a previous c larification from the USDA 1 and, in addition, that column E is reserved for animals for which pain- or distress-alleviating drugs are not used because of experimental needs. In this case there was no experimental need to withhold drugs, which the administrator said supported the use of column D. D o y o u t h i n k t h a t t h e IA C U C administrator’s explanation and actions were correct, or was the IACUC chairman right? Would you have taken any actions that were not taken by the Great Eastern IACUC?
rocedure is applied, that is, pain in excess p of that caused by injections or other minor procedures”2. The animal did not receive its daily dose of analgesia, and hence the veterinary medical care that was provided was i nadequate, in violation of USDA Animal Care Resource Guide Policy #3: Veterinary Care and Policy #11: Painful Procedures3. Policy 3 was v iolated in that adequate post-procedural care was not provided and the animal did not receive its once-daily a nalgesic dose. Policy 11 was violated in that the post-procedural analgesic regimen described in the IACUCapproved protocol was not f ollowed. Policy 11 states that “[a]nimals e xhibiting signs of pain, discomfort, or d istress such as weight loss, decreased appetite, abnormal activity level, adverse r eactions to t ouching inoculated areas, open sores/necrotic skin lesions, a bscesses, lameness, conjunctivitis, corneal edema, and p hotophobia are expected to receive appropriate relief unless written scientific justification is provided in the animal activity proposal and approved by the IACUC”3. The USDA annual report form i ndicates that categor y E should include the
“ number of animals upon which teaching, e xperiments, research, surgery or tests were conducted involving accompanying pain or distress to the animals and for which the use of a ppropriate anesthetic, analgesic or tranquilizing drugs would have adversely affected the procedures, results, or interpretation of the teaching, research, experiments, surgery, or tests.” Thus, we feel that the dog should not be placed in c ategory E, because analgesics were withheld as a result of human error and not for scientific reasons. There are two areas of concern: the lack of adequate veterinary care and training of the technical staff. We would have required the technical staff members to receive additional training to ensure they understand the importance of reading and following the IACUC-approved protocol, documenting all procedures and treatments in the animal’s medical record and notifying the attending veterinarian of any questions or problems.
Volume 43, No. 10 | OCTOBER 2014 347
1. Brown, P. & Gipson, C. A word from OLAW and USDA. Lab Anim. (NY) 38, 347 (2009).
1. Brown, P. & Gipson, C. A word from OLAW and USDA. Lab Anim. (NY) 38, 347 (2009). 2. Animal Welfare Regulations. 9 CFR. Chapter 1 Subchapter A,1.1 Definitions. 3. US Department of Agriculture. Animal Care Policy Manual (USDA, Riverdale, MD, 2014).
protocol review
Coan is the Attending Veterinarian and Director of the Office of Laboratory Animal Care, Adams is a Clinical Veterinarian in the Office of Laboratory Animal Care and Glass-Mattie is the Director of Animal Compliance Support at the University of Tennessee, Knoxville, TN.
Response Law does not address human error
npg
© 2014 Nature America, Inc. All rights reserved.
Alison D. Pohl, MS, MT, rLATg, CPIA & Ron G. Wallace, PhD, CIH, RBP
In evaluating this scenario, we assume that the analgesia schedule called for more than 1 day of analgesics, meaning that the animal may have experienced a higher degree of pain than anticipated because of the missed dose. But analgesics were given, and so it is appropriate to place the animal in category D on the USDA annual report. There are limitations to the quality of data provided on the annual report. Pain experienced by animals can be c ategorized as no or momentary pain, pain relieved by administration of analgesics or pain not relieved by administration of analgesics because their use would adversely affect the research results. It would be difficult to j ustify the placement of these animals in category E, because analgesics were given, albeit late, and the delay was a result of human error and not an IACUC-approved action. Great Eastern’s IACUC concluded that this was an unfortunate error and no sanctions were considered necessary. This denotes an attitude of acceptance and complacency toward human error. It would be nice if there were no mistakes when using animals for research, testing or training; unfortunately, that is not likely to ever be the case. Its inevitability, however, does not mean that human error should not be addressed. Great Eastern’s IACUC should have required the investigator responsible for the research to submit a plan of action to ensure the appropriate administration of analgesics in the future. This plan could include c onfirmation checks such as checklists, a buddy system or supervisor sign-off to rocedures make sure that all required p are completed. Confirmation is especially important when a m istake could lead to
348 Volume 43, No. 10 | OCTOBER 2014
unnecessary pain or distress to animals, the minimization of which is one of the main focuses of animal welfare in research. The IACUC must find a b alance between t aking the trouble to ensure that procedures are done correctly and living with mistakes. Will the overall results be better if we aim to make no mistakes (but probably make a few istakes anyway) or if we just accept that m are going to happen and pay the price when they do? Each IACUC should determine what an acceptable balance is and how to bring personnel up to the appropriate level of rigor required to strike that balance. It is the IACUC’s responsibility to set the standard. Pohl is IACUC Coordinator and Research Compliance Monitor and Wallace is Biological Safety Officer and IBC Coordinator at UConn Health, Farmington, CT.
Response What’s right? Yolanda P. Villarreal Acosta, BA
The IACUC administrator should have provided an explanation of how the USDA pain and distress categories are assigned. The focus in this scenario is whether the animal’s experience of more than m omentary, pain or distress was relieved (category D) or not relieved ( category E)1. As the IACUC chair expressed, category E is appropriate because the animal experienced pain prior to relief: “Animals must be listed in Column E if they are s ubjected to painful procedures and the anesthetics, analgesics, tranquilizing drugs or other palliative treatment did not adequately preclude more than slight or momentary pain or distress”1. The IACUC Guidebook states, “It is the responsibility of the IACUC to c ritically e valuate all research protocols for the potential to cause pain or distress and assess the steps that are to be taken to enhance animal well-being”2. In this s cenario, the lab technicians took the f ollowing steps: a dminister daily analgesia; realize that a dose was missed; reinitiate analgesia schedule; contact the IACUC. If there were no f urther steps in the approved protocol for the lab technicians to follow, then the IACUC should re-e valuate the protocol
and ask the i nvestigator responsible for the research to discuss with the attending v eterinarian further steps to be taken, such as r ecording details of analgesic administration (technician, time, dose, etc.); monitoring animals more than once per day and d ocumenting this m onitoring; and having the investigator or other d esignated individual confirm that duties are c ompleted. If the d esignated i ndividuals are unable to monitor an animal or provide a scheduled treatment, then arrangements can be made with the veterinary staff to ensure this task is done. The protocol should also include guidance on managing a missed dose and list criteria that warrant intervention by the attending v eterinarian, who should have been immediately contacted along with the IACUC. The IACUC should have also considered re-training the staff members to confirm that the lab technicians and the investigator understand the privilege of working with research animals. The IACUC may require that the investigator submit a follow-up report and that the lab documentation be checked by the IACUC during semi-annual laboratory inspections. Staff members should be reminded that the veterinary staff and IACUC office are available and should feel comfortable contacting either group for assistance at any time. With everyone working together to ensure that research animals receive the proper care, compliance can be maintained while research is carried out responsibly. Finally, the IACUC, upon being notified of the incident, should have phoned OLAW and USDA to alert them of the incident prior to sending the formal report to OLAW. The USDA inspector will evaluate the report d uring the annual inspection of the institution. 1. Office of Animal Care and Use. Guidelines for Preparing USDA Annual Reports and Assigning USDA Pain & Distress Categories (National Institutes of Health, Bethesda, MD, 2013). 2. ARENA/OLAW. Institutional Animal Care and Use Committee Guidebook 2nd edn. (Office of Laboratory Animal Welfare, Bethesda, MD, 2002). Acosta is Research Compliance Coordinator for the IACUC, IBC, CSC & R&LSC in the Office of Research Integrity, Office of the Vice President for Research at the University of Texas at San Antonio.
www.labanimal.com
