An important refinement that should be implemented whenever possible is the use of early endpoints, that is, ending the experiment at the earliest point that the desired data can be collected and before the animals are subjected to unnecessary pain and distress. Preferably, death should be avoided as an endpoint for animal experiments. Alternatives to death as an endpoint, such as behavioral changes, fluctuations in body temperature, HID50 (hypothermia-inducing dose 50 as opposed to LD50) should be sought. Body condition scoring and weight loss patterns should be taken into consideration and evaluated to determine whether they can be implemented as a refinement. Pilot studies should be conducted under veterinary supervision whenever a novel procedure is planned that has the potential to be painful or distressful. For procedures that are known to be painful without the benefit of analgesics (e.g., sternal thoracotomy), pain-relieving drugs should be used preemptively.
As we all agree, to optimize the humane treatment of laboratory animals, more research is needed in the area of recognition and assessment of pain and distress.
DR. KARAS (Alicia Karas, Tufts University): With regard to your statement that analgesics and anesthetics could interfere with research results, I think the important point is that we understand quite well the effects of anesthetics and analgesics. However, the big unknown is how pain and distress affect research results. It appears to me that aspect of the issue should be included in the statement.
DR. COUTO: Your point is excellent. For the sake of clarity, this issue was addressed by the Scientific Advisory Committee and was included in the position statement. I did mention before that pain and distress, as well as the drugs used to alleviate them, can interfere. As a corollary to that, I should say that the effect of the drugs as well as the effects of the pain should be assessed or evaluated at least in a limited pilot study.
DR. ANDERSON (Lynn C. Anderson, Merck Research Laboratories): You said that animal reporting is the responsibility of the IACUC and the attending veterinarian, but you did not mention the investigator. I believe it is very important to stress that there is a real partnership between the investigator, the attending veterinarian, and the IACUC to monitor pain and distress; and that the burden is not on just the IACUC, the attending veterinarian, or the investigators, as suggested earlier.