IACUC Protocol Review

Protocol review by the IACUC is an essential element of the oversight of research with animals, which is subject to detailed requirements from a variety of regulatory and accreditation sources. Investigators and IACUC members may find it daunting to keep track of all these requirements and may worry about forgetting or misinterpreting something, which could land them or their institutions in trouble. This module provides a comprehensive overview of the regulations and available guidance that apply broadly to protocol review in the United States. This module also helps to put documents into historical context and clarify their applicability.

Recommended Use: Required
ID (Language): 20366 (English)
Author(s): Carole R. Baskin, DVM, MSc - Saint Louis County Department of Public Health

This module provides learners with a review of what the IACUC must do with animal use protocols. Learners will explore who must do the review, as well as when and how often the IACUC must review and approve protocols. A discussion of the methods the IACUC may use to review animal use protocols and the criteria the IACUC must use in reviewing and evaluating protocols provides learners with a detailed review of these critical IACUC elements.

Recommended Use: Required
ID (Language): 20367 (English)
Author(s): Michael D. Mann, PhD - University of Nebraska Medical Center - Emeritus

The regulatory requirements for the use of animals in research, teaching, and testing address all aspects of animal care and use, including the justification to use animals for proposed research goals. Investigators generally frame justifications in terms of the relative value of the benefits to humans and other animals compared to the relative costs to the animals in the research, along with the importance of the choice of species to the value of the results. Consequently, regulations require investigators to ensure, and IACUCs to validate, the use of animals to prove a concept that is beneficial to humans and/or animals before a project begins. In this module, learners will explore the regulatory references that require appropriate justification for animal use in research. They will also review the standards the IACUC must apply in evaluating justifications for animal use in research.

Recommended Use: Required
ID (Language): 20368 (English)
Author(s): Lauren Danridge, BA, CPIA, LSSS, SSGB - University of Michigan; William Greer, BS, CPIA, LAT, CM - University of Michigan

As part of their responsibility to review all activities involving animals, IACUCs must evaluate the experience and qualifications of individuals performing the procedures described in a protocol. To ensure the proper care of animals and use of good scientific methods, it is essential for the individuals who work with animals in research, teaching, and testing to be proficient in the procedures they perform. This module presents the relevant regulations and guidance documents associated with personnel qualifications.  Learners are guided through a discussion on training the research team, the elements of training, and evaluating individuals involved in the protocol who may require specific training. Through this module, learners will be able to describe ways to evaluate the adequacy of individuals’ qualifications to perform procedures described in the protocol application.

Recommended Use: Required
ID (Language): 20369 (English)
Author(s): Deyanira Santiago, MBA, RLATG - The Wistar Institute

Evaluating pain and distress in research is a critical component of any research protocol. This module discusses evaluating a protocol for the level of pain and distress an animal may experience. It covers the applicable U.S. regulations and guidelines related to pain and distress, including the U.S. Department of Agriculture (USDA) pain and distress categories, as well as the IACUC’s responsibilities for reviewing proposed animal activities involving pain and distress. It also provides an overview of managing expected pain in surgical and non-surgical procedures and the importance of research team communication, coordination, and training. The module also includes species-specific indicators of pain and distress, intervention strategies, and information on humane endpoint determination.

Recommended Use: Required
ID (Language): 20370 (English)
Author(s): Elizabeth Nunamaker, DVM, PhD, MS, DACLAM, DACAW - University of Florida, Animal Care Services; Sylvia Singletary, DVM, MBA, DACLAM - Consulting Laboratory Animal Veterinarian

Alternatives to the use of animals in research have long been of interest. Investigators are continually looking for nonanimal techniques and systems to help advance knowledge. The public also has interests in ensuring the use of animals only when the value of the research justifies doing so. Both the scientific community and the public expect careful consideration of alternatives to the use of animals whenever relevant.

The topic of “alternatives” applies to every form of alternatives to research with animals: alternatives to working with animals at all, to working with large numbers of animals, and to performing specific types of procedures on animals. These correspond to the “3Rs” of animal experimentation, which are replacement, reduction, and refinement.

This module focuses on refinement and addresses alternatives to protocol procedures that may result in pain or distress in animals that is more than momentary or slight. The IACUC is responsible for evaluating whether the protocol’s documentation demonstrates that the investigator has adequately considered such alternatives.

Recommended Use: Required
ID (Language): 20371 (English)
Author(s): Mary Ellenberger, DVM, MS, DACLAM - Washington University School of Medicine

During protocol review, the IACUC must pay special attention to procedures involving potential pain or distress that investigators cannot alleviate. IACUCs must always carefully weigh animal welfare against potential research benefits, so procedures with potential for greater impacts on animal welfare also require special attention. This module discusses why certain procedures need special attention from the IACUC during protocol review, with emphasis on the evaluation of the animal’s welfare and compliance with regulatory requirements. It also explores what the IACUC must do when reviewing procedures that need special attention as well as specific factors to consider when animals undergo procedures that need special attention.

Recommended Use: Required
ID (Language): 20372 (English)
Author(s): Tom Zimmerman, DVM, MPVM, DACLAM - Stony Brook University

When working with hazardous agents in live animals, effective hazard identification and mitigation depend on coordination between the investigator, environmental health and safety office, occupational health and safety program (OHSP), and animal care and use program. The IACUC ideally will facilitate this coordination since the animal use protocol needs to identify any hazardous agents involved in the research. Each IACUC member has a role in recognizing when the protocol proposes to use hazardous agents and in evaluating, at a basic level, the health and safety impacts of those agents. The IACUC can then facilitate how the involved parties implement a comprehensive OHSP in compliance with the Guide for the Care and Use of Laboratory Animals (the Guide). In this module, learners will explore what to look for in a protocol as part of an accurate and efficient assessment of the risks associated with each category of hazard (biological, chemical, and radiation) and identify the regulatory and guidance documents that cover risks associated with hazardous agents proposed for use in animal research.

Recommended Use: Required
ID (Language): 20373 (English)
Author(s): Gabrielle Repik, MS, MHS, CBSP, CMAR, RLATG - Weill Cornell Medicine

It is the IACUC’s responsibility to oversee and evaluate the animal care and use program, including euthanasia procedures and other provisions for animals at the end of their involvement in a research protocol. Euthanasia is an important component of addressing pain and distress through humane endpoints and collecting research specimens upon reaching experimental endpoints. During protocol review, IACUCs should review the descriptions of experimental and humane endpoints to ensure they are consistent with ethical and regulatory requirements.

This module presents an in-depth discussion on euthanasia and its need in biomedical research. Learners will also explore why it is important to minimize distress during the euthanasia process and the role of an IACUC in reviewing euthanasia methods. The module also provides a discussion on some potential alternatives to euthanasia and concludes with an overview of the safety, security, and well-being of personnel who perform euthanasia.

Recommended Use: Required
ID (Language): 20374 (English)
Author(s): Jenny Kalishman, DVM, MS - University of Maryland School of Medicine

Endpoints are the conditions under which each individual experiment in a study will come to an end. Common determinations of endpoints are time and performance. These are experimental endpoints because they reflect the design of the experiment. However, there is a second set of endpoints to identify when the experiment must end for the sake of humane treatment of the animals, potentially before reaching the experimental endpoints. These humane endpoints are typically defined in terms of indicators of pain or distress in the animal, such as weight loss from inappetence, weight gain from tumor growth, species-specific behaviors, or physical condition. Setting the criteria for humane endpoints requires careful consideration of what the animals are likely to experience as a result of the experimental protocol and an understanding of how to interpret physical and behavioral changes as indicators of pain or distress. This module explores the differences between experimental and human endpoints and provides learners with factors that are involved in defining appropriate humane endpoints. The module concludes with a discussion on how investigators can refine experimental endpoints to minimize pain and distress.

Recommended Use: Required
ID (Language): 20375 (English)
Author(s): Carole R. Baskin, DVM, MSc - Saint Louis County Department of Public Health

The U.S. regulations include an oversight system to protect animals involved in the study of disease models and develop new forms of treatment for the benefit of society. In this module, learners will explore the considerations in harm-benefit analysis and the role of the IACUC in this process. The module discusses the relationship between the potential harms done to animals and the benefits expected from research as well as what investigators can do to decrease the potential harms or increase the expected benefits of a project.

Recommended Use: Required
ID (Language): 20376 (English)
Author(s): Michael D. Mann, PhD - University of Nebraska Medical Center - Emeritus

Science occurs in the present but is always looking to the future. Quality science often invites descriptions that imply extreme focus and intensity, such as “cutting-edge” and “ground-breaking.” Despite meticulous prior planning, however, scientific procedures involving animals often need amending as results emerge that provide new understanding.

This module discusses amendments, or protocol modifications, which are changes in IACUC-reviewed and -approved protocols. Learners will explore how to handle amendments for changing approved protocols based on the Office of Laboratory Animal Welfare’s Guidance on Significant Changes to Animal Activities. In addition, the module presents examples of amendments that may undergo pre-approved IACUC review methods and ways to determine which proposed protocol changes can occur using methods other than Full Committee Review (FCR) and Designated Member Review (DMR).

Recommended Use: Required
ID (Language): 20377 (English)
Author(s): Randall J. Nelson, PhD - The University of Tennessee, Health Sciences Center

In this last module, learners are presented several scenarios that will challenge them to evaluate sometimes incomplete information and determine whether the actions in the scenarios comply with regulatory requirements and are consistent with accepted standards.

Recommended Use: Required
ID (Language): 20378 (English)
Author(s): Randall J. Nelson, PhD - The University of Tennessee, Health Sciences Center