Response to Protocol Review Scenario: The time for active post-approval monitoring is now

The unexpected death of any research animal is troubling, but especially when it appears that a trend might be forming. While in the case of Osterman's research, only two animals have died, it is incumbent upon the IACUC to determine the root cause of these unexpected deaths. The IACUC must, to the best of its ability, determine whether the root cause is due to inadequate training (a situation likely to incur other deaths) or a non-procedural issue that is unlikely to incur additional deaths (e.g., an individual rabbit with undiagnosed cardiac disease). Osterman was correct in his timely reporting of the events before more unexpected deaths occurred. Rabbits are an “AWA-covered species.” In the spirit of open communication, the IACUC should report the two deaths to the USDA while clearly stating that current evidence does not point to a non-compliance at this time¹. Likewise, if the research is PHS-funded, OLAW should also be informed immediately². The IACUC should report any findings of their subsequent investigations to these same agencies.

To aid in the IACUC investigation, the institution's veterinarians exercised due diligence in performing the necropsies on the two rabbits. The lack of gross anatomic and histopathological findings lends support that the deaths were not due to underlying disease conditions or anatomic anomalies. Likewise, the anesthesia machines appear to be in working order. This lack of findings, however, does not rule out a possible role that the anesthesia might have played in these deaths. For example, hypercapnia associated with physiologic dead space in the anesthesia circuit may not necessarily show up on necropsy. A root cause cannot be determined from the present investigation. Thus, I believe the body of evidence does not support an immediate IACUC suspension of Osterman's research, but, instead, the IACUC should institute active post-approval monitoring (PAM) of Osterman's rabbit protocol.

The Guide states that PAM “helps ensure the well-being of the animals and may provide opportunities to refine research procedures”³. Neither the AWAR or the PHS policy refer to PAM specifically by name. PAM can take several forms. One is the so-called “passive” form which relies on investigator self-reporting and the IACUC review of any adverse events reported on the annual and triennial protocol reviews required by the AWAR and PHS Policy, respectively^1,2. In the case of Osterman's research, a more “active” PAM-approach is warranted because a potential procedural (and thus a training) issue with the implementation of the lab's rabbit-anesthesia protocol might be to blame. IACUC member(s) should observe the pre-anesthetic and anesthetic procedures from start-to-finish. At least one of the IACUC-appointed observers should be sufficiently knowledgeable in rabbit anesthesia. This could be one of the institution's veterinarians or an ad-hoc appointed observer, such as a board-certified veterinary anesthesiologist.

Should active PAM reveal deficiencies in the training and practice of anesthetic procedures as the root cause, the IACUC should suspend the protocol activities immediately¹. To remove the suspension, Osterman should provide the IACUC proof of successful retraining of all staff involved in the rabbit anesthesia procedures. Additionally, it is within the IACUC's purview to stipulate that a continuation of active PAM is required as a condition of protocol reinstatement.

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