The statistical power of studies for the assessment of side effects of toxicants on honeybees conducted according to current guidelines is often limited. A new test design and modified field methods have therefore been developed to decrease uncertainty and variability and to be able to detect small effects. The new test design comprises a monitoring phase (before the tunnel phase) for the selection of honeybee colonies and modified methods, which include assessments of colony strength, an evaluation of the cell content of all cells of hives using photos and digital analysis, and the use of video recordings for the assessment of foraging activity and forager mortality. With the proposed new study design and the modified field methods variability between hives was considerably reduced, which resulted in a marked reduction of the minimum detectable difference (MDD). This makes it possible to address the Specific Protection Goals defined by the European Food Safety Authority and to gain unprecedented insight into the development of hives and driving factors.