When is it required to submit an amendment to an existing protocol?

A Principal Investigator's (PI's) research plan may change and evolve while an approved study is in progress especially since protocols are often written and approved before the funding is obtained to commence work using animals. Public Health Service (PHS) Policy (IV,B,7) requires PIs to seek Institutional Animal Care and Use Committee approval for significant protocol changes. The Animal Welfare Act Regulations (AWAR) (§2.31,c,7) have similar language. Here at NYU the Institutional Care and Use committee is referred to as the "University Animal Care & Use Committee" or UAWC

Both the AWAR and PHS Policy require that the UAWC review and approve proposed significant modifications to ongoing activities using animals prior to initiation. The AWAR (§2.31,d,l) state that the UAWC shall determine that the proposed activities or significant changes meet requirements which are detailed at §2.31,d,l,i-§2.31,d,l,xi. These requirements include addressing pain and distress, alternatives to painful procedures, animal housing and veterinary care, personnel training and qualifications, surgical standards, and appropriate euthanasia techniques. PHS Policy IV,C,l,a-IV,C,l,g) states that the UAWC should review the animal-related components and determine that the proposed research projects are in accordance with PHS Policy, the Animal Welfare Act, the Guide to the Care and Use of Laboratory Animals, and the institution's Assurance with the National Institutes of Health/Office of Laboratory Animal Welfare using criteria similar to the AWAR unless acceptable justification for the departure is presented by the PI.

The protocol amendment process provides an opportunity for an investigator to refine his experiment and change an approved protocol at times other than when regularly scheduled continuing protocol reviews occur. From the PI's perspective the amendment process provides a relatively simple, straightforward, and timely method to make changes to a previously approved protocol, which facilitates research while keeping the UAWC apprised.

What activities can be considered appropriate for an amendment?
The UAWC is charged by the Federal and State Governments to consider its regulatory responsibilities when considering the best methods for reviewing proposed amendments (changes) to approved protocols. Whether the activity proposed can be a simple amendment or requires a rewritten protocol with regular UAWC review, depends upon whether the proposed change is considered to be minor or significant. Thus, ALL substantive protocol changes must be reviewed and approved by the UAWC, although less extensive changes may utilize the amendment mechanism rather than necessitating a complete rewrite of the protocol. An institution can permit alterations in administrative information to be changed without UAWC review (e.g., electronic mail address of the PI or a change in the funding agency).

The distinction between minor and major (significant) changes, involves assessing the potential or actual reduction in animal welfare and the change in the overall ethical cost-benefit ratio. In this view, the proposed amendment must be considered in conjunction with the original protocol to adequately determine if a significant change has been proposed. Protocol changes which are complex, or submissions of multiple sequential amendments to an existing protocol are not well suited to the amendment mechanism. If in doubt whether a proposed change is "significant" from the point of view of animal welfare, please call the University veterinarian or the Chair of the UAWC.

Please note: All changes to a protocol require the completion of the amendment form.

 

Examples of changes in animal use procedures that could affect animal welfare and are generally considered to be major (significant), therefore warranting UAWC review:

 

  • Change in purpose, specific aim or objectives of a study.
  • Switching from nonsurvival to survival surgery.
  • Change in protocol that would require an animal to undergo more than one survival surgery.
  • Change in protocol that would require animals to be fed, housed or cared for in a way that is not standard for that species, or does not meet that species' minimum requirements.
  • Increase in the degree of invasiveness of a procedure or discomfort to an animal.
  • Change in protocol that would eliminate or restrict an animal's access to veterinary care.
  • Change of species.
  • Addition of USDA-regulated species.
  • Significant increase in number of animals used over that projected: for example, an increase of 20% for projects approved for greater than 20 animals, or, an increase of 3 animals for projects approved for 6 to 20 animals, or, an increase of I animal for projects approved for 5 or fewer animals.
  • Anesthetic agent(s), the use or withholding of analgesics.
  • Change in methods of euthanasia.
  • The duration, frequency, or number of procedures performed on an animal.
  • Addition of survival surgery.
  • Addition of a painful procedure.
  • Change in protocol where death becomes the experimental end point. For purposes of this criterion, death is defined as natural death resulting from experimental conditions (rather than euthanasia at a time when a set of criteria recognized as the end point is met).
  • Unanticipated marked increase in clinical signs or proportion of animal deaths

 

Examples of changes considered to be minor:

  • Substitution, addition or deletion of personnel or collaborator, excluding principal investigator.
  • Addition of another strain of the same animal species
  • Change in sex of animal to be used
  • Small increase in animal numbers
  • Need to repeat an experiment
  • Addition of minor surgery
  • Addition of sample collection times
  • Additional noninvasive sampling
  • A change in procedure that is more specific than the language required in the original protocol does not require an amendment or UAWC approval, provided the change is not expected to increase pain or distress. (e.g., changes in needle gauge, surgical instruments, vehicle for injections, and use of post-mortem tissue.)
  • Replacing a procedure with another less painful, stressful or hazardous that achieves the same specific objectives
  • Changing experimental design to reduce the use of animals
  • Adding a comparable strain or treatment (e.g., Wistar to Sprague-Dawley; change in vector) if no change in pain, distress, or biosafety is expected.
  • Addition of a funding source
  • Removing a proposed experiment from a protocol.
  • Updating the alternatives section of a protocol (including Policy 12).
  • Changing or adding analgesia or anesthetic on veterinary recommendation.
  • Adding a procedure or treatment that is considered pain category “B” if the change does not significantly increase the numbers of animals approved or the duration of the study (e.g., add a nonstressful behavioral test).

 

When is minor amendment approval effective?
The UAWC Administrator may approve minor amendments after administrative review (and veterinary, or environmental services review when applicable) on behalf of the UAWC. Once approved, PIs may implement the change immediately. Minor amendment approvals will be listed in the minutes and any UAWC member can request a copy of the application, and/or full UAWC review. Approval for minor amendments will not be given if there are veterinary or administrative concerns or if the protocol has been associated with compliance violations within the past year.

 

Major Changes

 

Examples of change in animal use procedures that could affect animal welfare and are generally considered to be major (significant), therefore warranting a revision and rewrite of the protocol for UAWC review:

 

  • Change in purpose, specific aim or objectives of a study.
  • Switching from nonsurvival to survival surgery.
  • Change in protocol that would require an animal to undergo more than one survival surgery.
  • Change in protocol that would require animals to be fed, housed or cared for in a way that is not standard for that species, or does not meet that species' minimum requirements.
  • Increase in the degree of invasiveness of a procedure or discomfort to an animal.
  • Change in protocol that would eliminate or restrict an animal's access to veterinary care.
  • Change of species.
  • Addition of USDA-regulated species.
  • Significant increase in number of animals used over that projected: for example, an increase of 20% for projects approved for greater than 20 animals, or, an increase of 3 animals for projects approved for 6 to 20 animals, or, an increase of I animal for projects approved for 5 or fewer animals.
  • Anesthetic agent(s), the use or withholding of analgesics.
  • Change in methods of euthanasia.
  • The duration, frequency, or number of procedures performed on an animal.
  • Addition of survival surgery.
  • Addition of a painful procedure.
  • Change in protocol where death becomes the experimental end point. For purposes of this criterion, death is defined as natural death resulting from experimental conditions (rather than euthanasia at a time when a set of criteria recognized as the end point is met).
  • Unanticipated marked increase in clinical signs or proportion of animal deaths

 

Minor Changes

 

Examples of changes considered to be minor and are generally well-suited to the amendment mechanism:

  • Substitution, addition or deletion of personnel or collaborator, excluding principal investigator.
  • Addition of another strain of the same animal species
  • Change in sex of animal to be used
  • Small increase in animal numbers
  • Need to repeat an experiment
  • Addition of minor surgery
  • Addition of sample collection times
  • Additional noninvasive sampling
  • A change in procedure that is more specific than the language required in the original protocol does not require an amendment or UAWC approval, provided the change is not expected to increase pain or distress. (e.g., changes in needle gauge, surgical instruments, vehicle for injections, and use of post-mortem tissue.)
  • Replacing a procedure with another less painful, stressful or hazardous that achieves the same specific objectives
  • Changing experimental design to reduce the use of animals
  • Adding a comparable strain or treatment (e.g., Wistar to Sprague-Dawley; change in vector) if no change in pain, distress, or biosafety is expected.
  • Addition of a funding source
  • Removing a proposed experiment from a protocol.
  • Updating the alternatives section of a protocol (including Policy 12).
  • Changing or adding analgesia or anesthetic on veterinary recommendation.
  • Adding a procedure or treatment that is considered pain category “B” if the change does not significantly increase the numbers of animals approved or the duration of the study (e.g., add a nonstressful behavioral test).