Dr. Peter Alley, a thoracic surgeon, was seeking IACUC approval for a postoperative drug treatment that had the potential to be toxic to rats, the animal model that was being used. The toxicity was similar to that experienced by humans undergoing the same surgery and needing the same drug. Alley was using a modified dosage, dosing schedule, and infusion rate, which he hoped would dramatically decrease the drug's toxicity. His pilot study suggested that toxicity would be insignificant, but now, with the use of more animals, there was always the potential for a problem.

Alley knew he would have difficulty providing overnight observations of his animals, but he assumed that the IACUC might want to know why this was not occurring, because the first 24 h after use was the known time frame for the drug's toxicity. However, he provided data from humans and animals that indicated that about 85% of all toxicity (with the unmodified dosage and schedule) actually occurred within the first 12 h. Based on his pilot study, he didn't think there would be any toxicity at all. Nevertheless, for the first 12 h he would have somebody observing the animals at least every 30 min. Because recovery from toxicity almost never occurred without significant medical intervention and toxicity treatment was not the objective of the research, he wrote that any animal showing certain defined signs of toxicity would be immediately euthanized.

Also, because the surgery necessitated a thoracotomy, it might seem that someone would have to provide analgesia during the night. To allay that issue, he wrote that the surgery would be performed at about 9 a.m., with the analgesic buprenorphine being administered an hour before the induction of anesthesia. The procedure itself would take only about 15 min, and another analgesic, bupivacaine, would be infiltrated near the surgical incision before closure. The intravenous infusion of the study drug would follow surgery, every 15 min for the next hour. There would be administered a second dose of buprenorphine in the mid-afternoon (about 3 p.m.), a third dose about 9 p.m., and a fourth dose at about 7 a.m. the following day.

The IACUC debated the need for overnight observations of the rats. One group said that because the study was intended to assess toxicity, there was enough reason to have the animals observed throughout the night and euthanized if necessary. They also felt that there might be a need for an additional dose of buprenorphine during the night. Other members of the IACUC believed that Alley had adequately covered all reasonable contingencies and even had a preliminary study completed to strengthen his position. They said that on the first postoperative day it was not very unusual to have a rat die, whether treated with a potentially toxic drug or not, and if Alley was required to monitor his animals overnight, they might as well do the same for all rodent surgeries.

Did Alley make a sufficiently strong argument, or do you think that there is justification for overnight monitoring for the rats in this study? Are there any other approaches to be considered?

Response to Protocol Review Scenario: Yes (and no)

Response to Protocol Review Scenario: Not in this case

Response to Protocol Review Scenario: Proposal justified