Pain and Distress: USDA Perspective
W. Ron DeHaven
Deputy Administrator, Animal Care
I want to extend my thanks to ILAR (especially Dr. Ralph Dell) and to OLAW, NIH, for cosponsoring this meeting. Clearly, pain and distress is an issue looming very large on the horizon. It has been smoldering for approximately 5 years, but I suspect it will become very active in the next 3 to 5 years. USDA is here to listen because we will be dealing with this issue very actively in the immediate future. We will need to deal with the following aspects of the issue:
Because the focus in the past clearly has been on pain and far less on distress, we need to develop a definition of distress. The definition must work both for the biomedical research community and from a regulator's standpoint.
Alternatives to painful and distressful procedures must be considered, as required by the Animal Welfare Act and, of course, in the regulations that implement the Act.
To require minimization of pain and distress presupposes that one can recognize pain and distress in animals when it occurs.
There is much discussion now about our current pain and distress categorization system and whether it should be revised.
We cannot talk about any of these things without also considering the potential impact if the USDA should decide to regulate rats, mice, and/or birds. The burden that would be imposed would not be confined to regulating those species, but also would involve minimizing pain and distress in those animals and imposing reporting requirements because they represent 90% or more of the animals being used in biomedical research.
We have just revised Policy 12 (Table 1 and Appendix A) after a considerable amount of discussion and controversy. This policy, which requires consideration of alternatives to painful and distressful procedures, states that the database search remains the most effective and efficient method of satisfying the requirement of considering alternatives to painful and distressful procedures. At the same time, it recognizes that this method might not always be the best, or it might be one of multiple methods, used to satisfy the requirement. We believe the test should be applied by the IACUC as well as our inspectors and is two-fold. The first part of the test involves whether there is enough information for the IACUC to make a determination as to whether the principal investigator has made a good faith and reasonable effort to determine what alternatives are available. The second part of the test focuses on whether adequate consideration was given to bona fide alternatives that were identified.
Policy 11 relates to the minimization of pain and distress and reporting the same. We are in the process of revising that document. Clearly, whatever we produce is going to focus on minimizing pain and distress to the extent practical, as does the AWA and the regulations, and it will also include a definition of distress.
The draft version of this policy (Table 2 and Appendix A) recognizes that there might be other methods of relief besides anesthetics, analgesics, and tranquilizers. For example, there may be therapeutic agents (e.g., antibiotics) that in a disease process would provide some relief from pain and distress. In addition, other chemical agents or methods may provide relief from pain and distress.
The new policy will recognize that any given procedure (complete Freund's adjuvant might be an example) can be appropriately categorized in our current system under column C, D, or E, depending on the circumstances of how it is employed. On a retrospective evaluation of each animal on a case-by-case basis, it is certainly possible for some procedures to be categorized appropriately in any of the three current categories. Prospective reporting is acceptable, and retrospective reporting will clearly be allowed. As we currently have it drafted, this new Policy 11 would include descriptions of the three columns as found in our annual report. It would provide examples of what types of procedures would be categorized appropriately in each of those columns.
TABLE 1 Policy 12: Consideration of Alternatives
TABLE 2 Policy 11: Minimization of Pain and Distress—Draft
This definition of painful procedure is direct from the regulations: “Any procedure that would reasonably be expected to cause more than slight or momentary pain or distress in a human being to which the procedure was applied, that is, pain in excess of that caused by injections or other minor procedures.” The definition of distress in the current version of the rewrite of Policy 11 is as follows: “A state in which an animal cannot escape from or adapt to the external or internal stressors or conditions that it experiences resulting in negative effects upon its well-being.” We certainly welcome your comments on this working definition of distress. This definition of distress is for AWA purposes. No doubt there are other scenarios and situations where this definition of distress might not be appropriate.
We believe that the definition of distress for AWA purposes must be in excess of that which an animal would experience by routine husbandry or handling practices. In other words, simply caging an animal in a laboratory would not be considered distress in the context of the AWA and our regulations. Additionally, to distinguish stress from distress is critical in that the requirements for minimization of pain and distress apply to “distress” and not to “stress.”
We believe adherence to Principle IV of the US Government Principles is important and have included it in our working draft of the policy. It states that unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings will cause pain or distress in animals.
I mentioned earlier the concept of prospective versus retrospective reporting. Prospective reporting of pain or distress involves classifying animals in categories based on anticipation or expectation that the animals are likely to experience pain or distress and whether one plans to use any of the pain-relieving medications. In contrast, retrospective reporting is based on the actual observed presence or absence of pain or distress and the actual use or nonuse of pain-relieving measures.
EXPLANATION OF CATEGORIES
The descriptions we may include in a policy will not necessarily mimic or restate what the regulations state because the purpose of a policy is to provide clarification of the existing regulation. We hope that the following explanations and examples (among many) of the various categories will clarify these categories.
Description: Testing, teaching, or experiments involving no pain, distress, or use of pain-relieving medications. Again, recognize that pain or distress must be more than slight or momentary to be, by definition, a painful procedure.
Example: Collection of a blood sample from a peripheral vein not resulting in pain or distress. The animal remains calm throughout.
Description: Testing, teaching, or experiments involving pain or distress for which appropriate analgesic, anesthetic, or tranquilizing drugs are used.
Examples: (1) Use of an anesthetic agent to prevent pain or distress associated with intercardiac blood collection or perhaps any number of other types of procedures. (2) Use of a therapeutic agent to remedy an intentionally induced disease process. It would be a bit of a leap from where we are now, since current regulations recognize only anesthetics, analgesics, and tranquilizers or other pain-relieving medications as a means to appropriately classify procedures in Column D.
Description: Teaching, testing, or experiments involving pain or distress for which the use of appropriate anesthetic, analgesics, or tranquilizing drugs would have adversely affected the procedure 's results or the interpretation.
Examples: (1) Collection of an intercardiac blood sample without the use of pain-relieving medications. (2) Presence of an experimentally induced disease process that causes pain or distress that is not relieved by the use of pain-relieving medications.
As I mentioned, there is a much discussion about our current pain and distress categorization scheme and whether it accomplishes what we want to accomplish. Clearly, there is a diversity of opinion on what we are trying to accomplish, and I suspect we will hear some of those opinions later today.
TABLE 3 Gaps in the Current System
aP/D, pain and/or distress.
Listed in Table 3 are some of the gaps or areas where we think our current system may not be adequate and therefore may provide a reason for changing those categories. First, the pain and distress classifications reported are a mixture of prospective expectations, or prospective reporting of pain and distress, and retrospective reporting based on actual observations. Maybe this is as it should be, a mixture; or maybe it should all be retrospective reporting. This is one of the areas where we need to have some dialogue.
The current system does not differentiate between pain and distress. Maybe it is not necessary that we do; maybe we should. Again, I think this debate is an area for dialogue.
It does not officially recognize pain-relieving measures other than the use of anesthetics, analgesics, or tranquilizers. Clearly, other methods, whether they are chemical or nonchemical, have the potential to reduce or alleviate pain or distress.
The effectiveness of the pain and distress relief that is utilized is not addressed. So, to provide a ridiculous example, one could perform thoracic surgery on an animal, provide postoperative analgesia consisting of an aspirin, and perhaps appropriately categorize that in Column D. I think that is subject to debate, but there is nothing in the regulation that requires any evaluation of whether a particular pain and distress relief was effective.
Timeliness is another issue. Is the pain-relieving medication given as soon as, or before, the animal actually perceives pain and distress, or does it occur afterward? If so, how long afterward?
The current system does not address intensity of pain or the duration of the pain or distress. I think it is important to recognize that an animal experiencing moderate pain for a prolonged period of time may need to be categorized differently from an animal experiencing intense pain but only for 1 or 2 seconds.
The final gap in the current system is slightly more difficult to understand. This complex issue has only recently come to light. Specifically, there is currently
no accurate category in which to place an animal that does not benefit from the use of pain-relieving medications but for which there was no prohibition to the use of pain-relieving medications. Column E is for procedures for which pain-relieving medications could not be used because it is expected that the use of those medications would result in inaccurate data or inaccurate interpretations of the data. This description is in contrast to the animal that may have experienced pain or distress, was not provided pain-relieving medication, but for which there was no prohibition to the use of those medications.
As I said at the beginning, our primary reason for being here today is to listen. We will also be publishing a Federal Register Notice to gather input from the public and all interested parties with regard to this whole process. We hope that you will voice your opinion and, in doing so, will propose a solution and justification for any solution that you might suggest.
When we publish this Notice in the Federal Register, which we hope will be very soon, we hope that you will comment. We are anticipating a 60-day comment period for the definition of distress as well as the concept of changing our current pain and distress categorization scheme.
There are several ways to contact us through the Federal Register Notice, which will include specific instructions. In addition, you may submit your comments: via email (email@example.com ), telephone (301-734-4981), or fax (301-734-4978). Otherwise, the several USDA folks in this audience will be listening in earnest to the discussions throughout the day.