Response to Protocol Review Scenario: Approve and monitor

Approval of the entire protocol is appropriate. Institutions receiving support from the Public Health Service (PHS) for research or teaching involving vertebrate animals must implement an animal care and use program that includes procedures for self-monitoring. This function is described in the Guide for the Care and Use of Laboratory Animals¹ (the Guide), which states that the IACUC is responsible for the “establishment of a mechanism for receipt and review of concerns involving the care and use of animals at the institution.” If the entire protocol is approved, Holmes is required to terminate the study if Phase II is not successful. It is the responsibility of the IACUC to ensure that these conditions are followed.

Post-approval monitoring is accomplished in several ways. The Institutional Animal Care and Use Committee Guidebook² suggests that research, veterinary and husbandry staff should be aware of approved procedures and the conditions of the approval. The IACUC can establish a climate of compliance and encourage prompt reporting of departures from the approved protocol. The IACUC may choose to employ a compliance specialist to ensure that procedures are consistent with protocol approval. Additionally, the PHS Policy on Humane Care and Use of Laboratory Animals³ (the PHS Policy) requires that the IACUC “inspect at least once every six months all of the institution's animal facilities.” During this semi-annual inspection, IACUC members must note any deviations from the approved protocol. Regardless of the mechanisms used to accomplish post-approval monitoring, I assume that Best America Pharmaceuticals has competent self-monitoring mechanisms in place and that if Holmes is observed conducting elements of Phase III without the establishment of an ED₉₀, this deviation will be observed and the IACUC would then be allowed to suspend the activity in accordance with the PHS Policy.

Some IACUC members wanted Holmes to report Phase II results prior to the initiation of Phase III. Because the Guide¹ requires that the IACUC meet only every 6 months, however, Holmes' research may be delayed inappropriately if the IACUC requires additional information prior to proceeding. Additionally, because the Phase III studies are dependant on the ED₉₀ data, there seems to be little motivation for Holmes to continue with Phase III if an ED₉₀ is not established in Phase II. Furthermore, the results from Phases I and II of the study will not alter the total number of animals utilized. Therefore, there seems to be little rationale for not approving the entire protocol.

Finally, although the presented scenario does not specify whether this is a true or modified LD₅₀ study, and the posed question does not hinge upon this specification, my institution would require a modified LD₅₀ study with defined intervention points unless there is strong scientific justification requiring a true LD₅₀.

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