Laboratory safety studies are often required as the first tier testing method assessing potential adverse effects of pest control products (e.g., insecticides or transgenic insecticidal crops) on ecologically/economically important groups of non-target organisms. Regardless of the test organism species selected and endpoints measured in these studies, an appropriate experimental design is required to ensure that the methods have a sufficient level of statistical power to detect a specified magnitude of hazards (or effects) of the concerned pest control product. Case studies on non-target organism testing with transgenic Bt crops will be presented to illustrate how Tier I laboratory safety testing is designed to optimize the statistical power for detecting a specified magnitude of non-target effects of the concerned pest control technology.