Rx: Observe, Do not Treat When is it Appropriate not to Treat?

Abstract

Development of a protocol for a nonclinical safety study to evaluate the safety profile of an investigational therapeutic, whether it is a toxicology or safety pharmacology study, must not be conducted in haste. The evaluation of this novel therapeutics relies on the integrated strategy developed by the scientific team, which may include the pharmaceutical company and the services of a contract research organization. All nonclinical study protocols involving the use of live animals require the inclusion of the Institutional Animal Care and Use Committee (IACUC) and staff veterinarians during the review of the study protocol. The team, as a whole, must endure a frank, honest, and open discussion regarding study design and animal welfare issues. All available information regarding the test material should be shared with all parties in a manner and time that allows for constructive protocol and treatment strategy development. The intent of nonclinical safety assessments is driven by both administrative guidelines from drug regulatory agencies and statutory (legal) controls of federal laws. In working with test articles, particularly for small molecules, the probability of unexpected findings is relatively high. The research team must maintain the highest standards of animal care throughout this process which is complicated by the fact that when animal health and welfare issues occur they must be remedied fast, efficiently, and transparently. We review the pitfalls of safety assessment strategies and offer some industry standard resolutions that may help to make the road to market a little easier. The paper is written based on small molecule development, but many of the points would also apply to biopharmaceuticals as well.