Best America Pharmaceuticals was developing a unique new drug for human patients to treat both the hyperphosphatemia and the hypocalcemia that often accompany chronic renal failure (CRF). There was even preliminary evidence from preclinical work with a surgically induced rodent model that the drug might partially reverse the nephrocalcinosis that can be seen in CRF. Prior to moving forward on the path to a new drug application, Best America decided to investigate the drug's efficacy in pet animals with clinical CRF. Although the rodent model was satisfactory for initial studies, the company wanted to evaluate the drug in spontaneous clinical cases before investing further in its development.

Perhaps Best America was thinking that at some point, it might seek to have the drug approved for veterinary use, but that was not part of the discussion when Best America met with Dr. Harry Reiss, chairman of internal medicine at the Great Eastern University College of Veterinary Medicine. The basic proposal from Best was that the company would sponsor a dose-finding study in laboratory dogs and then move on to a study involving clinical cases of CRF in client-owned dogs who had an urgent need for the new drug. Best would pay for the clients' veterinary fees and would provide a substantial payment to the College itself. The primary stipulations of the proposal were that the animals were to have periodic blood samples and, if able to withstand them, four renal biopsies, at 3-month intervals.

Reiss estimated that the College of Veterinary Medicine's small animal clinic saw at least one new case of CRF a week and often more than that, and so entering the minimum of 20 new cases requested by Best would not be a problem. He was somewhat concerned about the need for kidney biopsies, but the company had said that there could be two biopsies from each kidney. That, he rationalized, was acceptable. The agreement with Best was tentatively completed pending approval from the IACUC, which at Great Eastern served its primary purpose and also approved clinical studies with client-owned animals.

The IACUC understood the potential value of the new drug and the need for the dose-level study, but it could not understand how the four biopsies would benefit the patients. It questioned why Reiss could not use blood samples to assess serum phosphorus and calcium levels. The committee also noted that there are non-invasive procedures to help evaluate kidney function. When pressed for an explanation, Reiss said that the biopsies were to help Best obtain a sequential picture of renal histopathology and tissue enzyme activity, neither of which could be determined without the biopsies. Additionally, Reiss reminded the IACUC that the ultimate goal was to develop a drug for people with CRF, which would likely have a useful application in animals with the same disease. Best America was not willing to sponsor the project without the biopsies, and if the project fell through, he said, both humans and animals would suffer until Best America located another school willing to collaborate in this important study.

There was a heated IACUC deliberation, largely focused on the need for the biopsies in client-owned animals. Do you believe the proposed study should be done under the general conditions prescribed by Best America? Or should the IACUC withhold its approval of the study?

Response to Protocol Review Scenario: Forget Fido

Response to Protocol Review Scenario: Modifications required

Response to Protocol Review Scenario: A dog is a dog