Experimental design principles include having a clear question, using comparisons and controls, replication, randomization, stratification, and factorial experiments. Good experimental design aims to be unbiased through randomization and blinding, precise through replication and blocking, simple to avoid mistakes, and able to estimate uncertainty through replication and randomization. Sample size is determined based on the desired power, significance level, measurement variability, and size of the expected effect. Consulting experts can help design efficient experiments that use animals ethically.