Principal Investigators and IACUCs… Post–Approval Protocol Compliance

Principal Investigators and IACUCs… Post–Approval Protocol Compliance Barbara Smith Laura Kandziolka Linda Callahan Dana-Farber Cancer Institute

Protocol Compliance Monitoring • Long recognized requirement, but rarely exercised. • No effective manner to tie the requirements of the rules and regulations to responsibilities of the institution, skills of the individuals, and the ability of the program to effect any change.

Protocol Compliance Monitoring • An ongoing program to audit approved animal protocols is an essential component of a comprehensive animal care and use program.

Protocol Compliance Monitoring • It provides an excellent method of ensuring institutional regulatory compliance, facilitating research activities, and giving investigators an opportunity to discuss concerns or changes needed in active protocols and the animal care program.

Protocol Compliance Monitoring • Why is it important? • To assure the well-being of animals in research and teaching activities. • To assure that activities are conducted in compliance with the regulations and standards (USDA, AAALAC, FDA, etc.). • To assure activities are consistent with and conducted in compliance with IACUC approved protocols.

Protocol Compliance Monitoring • Principal Investigators must realize that proper oversight leads to good animal care and good science, and that all parties concerned are on the same team with interests in the well-being of the animals and the success of the project.

Protocol Compliance Monitoring • The protocol monitoring process also provides the opportunity to meet with personnel actively engaged in animal-based research, giving a personalized review of relevant and/or new IACUC policies, observation of techniques, and provision of specific training.

Protocol Compliance Monitoring • The goal of compliance monitoring is to work with and support the research staff member, and to confirm accurate and consistent protocol performance in a collegial and unobtrusive manner. • Termed “Compliance Liaison Program” by Duke University.

Protocol Compliance Monitoring • Rules and regulations, while intended to be supportive of the research community and protective of the animal subjects, can become disruptive of ongoing research efforts. • The institution has provided assurance to the federal government and funding agencies that it will remain in full compliance with all rules and regulations.

Protocol Compliance Monitoring • The research community must learn to view compliance as a tool to facilitate their research objectives, assure their privilege for continued animal use, and a defense against allegations of misconduct.

Protocol Compliance Monitoring • Strategic plan: • Develop an auditing process to identify program deficiencies • Develop a methodology to evaluate trends in deficiencies • Partner with the IACUC to assess concerns and resolutions

Protocol Compliance Monitoring • Strategic plan (cont’d) • Use the trends in deficiencies to develop a focused training program. • Audit the process and progress, adjusting as necessary as new problems arise and old problems are resolved.

Protocol Compliance Monitoring • Goal of Compliance Liaison: support of the research staff and protection of animal subjects by confirming accurate and consistent IACUC approved protocol performance of animal based research in a collegial and unobtrusive manner.

Protocol Compliance Monitoring • Protocol noncompliance indicates that procedures or policies approved by the IACUC are not being followed: • Unauthorized surgeries • Unauthorized persons • Unauthorized drug use

Protocol Compliance Monitoring • Roles and Responsibilities: • Investigator and laboratory staff – will comply with requests for compliance monitoring from the IACUC. • Compliance Liaison – will work with the investigator and laboratory staff to observe activity, prepare accurate reports, provide recommendations for maintaining compliance, and provide necessary training.

Protocol Compliance Monitoring • Selection of protocols to review: • All active protocols involving the use of USDA Category D or E are monitored at least once annually. • Approximately 33% of the protocols involving less invasive procedures (USDA Category C) are monitored once annually.

Protocol Compliance Monitoring • USDA Category C: “Animals upon which teaching, research, experiments, or tests were conducted involving no pain, distress, or use of pain-relieving drugs.”

Protocol Compliance Monitoring • USDA Category D: “Animals upon which teaching, research, experiments, or tests were conducted involving accompanying pain or distress to the animals and for which appropriate anesthetic, analgesic or tranquilizing drugs were used.”

Protocol Compliance Monitoring • USDA Category E: “Animals upon which teaching, research, experiments, or tests were conducted involving accompanying pain or distress to the animals and for which appropriate anesthetic, analgesic or tranquilizing drugs would have adversely affected the procedures, results, or interpretation of the teaching, research, experiments, surgery or tests.”

Protocol Compliance Monitoring • Approved protocols should be prioritized for monitoring by the IACUC and/or Compliance Liaison to determine the frequency and order of monitoring based on: • Potential for pain and distress • Significant personnel changes • Current protocol activity • Species

Protocol Compliance Monitoring • “For cause” monitoring may be conducted at any time, with or without advance notice to the Principal Investigator.

Protocol Compliance Monitoring • Problems or deficiencies noted on these visits will be corrected at the time the deficiency is noted and further education and/or training will be provided, if needed. • A summary of these visits, and actions taken to correct deficiencies, will be reported to the IACUC at the next monthly meeting.

Protocol Compliance Monitoring • Compliance Liaison a voting member of the IACUC? • Recent COMPMED survey – 2/3 of responders said “no,” 1/3 said “yes.” • Majority of responders did not see voting status as a conflict of interest. • Most had Compliance Liaison as non-voting member.

Protocol Compliance Monitoring • Compliance Manager at Dana-Farber Cancer Institute: • Voting member of IACUC • Reports all compliance issues as a standing agenda item at monthly IACUC meetings • Reports to the Director of Animal Resources Facilities (DVM).

Protocol Compliance Monitoring • Dana-Farber IACUC reviews approximately 180 protocols per year • Has ~ 230 active protocols • 99% rodents (mostly mice). • Primates housed off-site under collaborating agreements with primate facilities.

Protocol Compliance Monitoring • Process of monitoring: • 1. Compliance Liaison shall attempt to make an appointment for the first non-compliant visit, or for routine visits. • 2. The Compliance Liaison must have a thorough understanding of the investigator’s approved protocol, including personnel and procedures listed (including surgery and euthanasia methods).

Protocol Compliance Monitoring • 3. Other issues or concerns: • Training of laboratory personnel • Supporting documentation of animal care, post-operative care or other study procedures. • Proper use of anesthetics and analgesics. • Survival surgery performed aseptically.

Protocol Compliance Monitoring 3. Other issues or concerns (cont’d.): • Safety concerns for humans and/or animals. • Presence of outdated drugs and/or supplies. • Calibration of anesthetic equipment. • Evidence of animal misuse, mistreatment, or neglect.

Protocol Compliance Monitoring • 4. Process of Reporting Information Concerning the Review: • When possible, the Compliance Liaison should discuss monitoring results with the Principal Investigator and other participating lab personnel before leaving the lab.

Protocol Compliance Monitoring • 4. Process of Reporting Information Concerning the Review (cont’d): • Animal welfare concerns should be immediately referred to the Attending Veterinarian. • The Compliance Liaison should send a written draft report of monitoring results to the PI.

Protocol Compliance Monitoring • 4. Follow-up Process (cont’d.): • The Compliance Liaison should send a final written report of the monitoring results to the Principal Investigator, lab personnel, IACUC Chair, and Attending Veterinarian.

Protocol Compliance Monitoring • 4. Follow-up Process (cont’d): • The Compliance Liaison should follow up on any issues that require protocol modifications, orientation of new personnel, or training. • Additional monitoring sessions may be part of the follow-up process to assist with proper corrective actions.

Protocol Compliance Monitoring • 5. Process of Addressing Concerns: • Investigators who disagree with monitoring results and/or recommendations may appeal to the IACUC.

Equine Tendon and Ligament Disorders A.J. Kaneps, D.V.M., Ph.D. Diplomate, ACVS

Principal Investigators and IACUCs… Post–Approval Protocol Compliance