1. Advantages of Conducting a Stand-Alone Respiratory Safety Pharmacology Study
Dennis J. Murphy, PhD, DABT
Director - Safety Pharmacology US
GlaxoSmithKline Pharmaceuticals

2. Advantages
Ventilatory measurements in animal models can be highly variable due primarily to a sensitivity to environmental changes (stimuli)
Stimuli include noise, odor, movement, handling, light, temperature
As such, measurements require a highly controlled environment for accurate and repeatable measurements
This can be achieved in a stand-alone study
Very difficult to achieve in a typical toxicology study where many activities are constantly ongoing and high number of animals are involved
Stand-alone studies allow the use of animals with a telemetry implant for measuring body temperature and pleural pressure (required to obtain a direct measure of airway resistance)
Generally not acceptable in a toxicology study due to pathology complications and resource limitations

3. Advantages (continued)
Stand-alone studies have greater flexibility in study design
Can use either crossover designs (animals serve as their own control) or parallel design with n = 6-8 of single sex per dose group
Can include recovery time for assessing reversibility or delayed effects (beyond 24 hrs post dose)
A typical 2/4 week toxicology study can be limited to a parallel design with n=3/sex per dose group (non-rodent) (sufficient for statistical analysis?) and may not include a recovery period (rodent or non-rodent)
Acute (day 1) measurements can be obtained with stand-alone studies
Day 1 measurements are critical because of tachyphylaxis or tolerance/compensation that can develop on repeat dosing
This can be difficult in toxicology studies because of TK analysis and enhanced clinical observations that need to be conducted on day1