The comparative power of the discriminant methods used in toxicological pathology.
It is highly desirable to use experimental methodologies in toxicological pathology that combine statistical power, practicality, and objective reviewability to detect small differences. The different ways of gathering data at the microscope can result in clear differences in power to discriminate small, but real, differences between treated and control rodent groups with nonneoplastic lesions. Six alternative methods of gathering and analysing results are compared. They are referred to as the Measuring, Ordering, Scoring (or Grading), Pair-contrast, Outside-control, and Affected methods. Measuring and Ordering methods are uniformly more powerful than other more common and highly esteemed methods, such as Scoring/Grading. From the practical perspective, Measuring and Ordering can be applied objectively, reviewed objectively, and interpreted to standards that are widely accepted as valid throughout experimental science e.g., using confidence limits and intervals. They also are intuitively natural extensions of routine toxicological histopathological examinations. Establishing a small difference between control and treated groups is commonly a problem when reporting no-observed-effect levels. Ordering is the recommended method for assessing if a small difference between treated and control groups is within chance variation or is the result of a true treatment effect, when measurement is impractical.
Holland
Tom
T
AstraZeneca Research and Development, SE-151 85 Södertälje, Sweden. Tom.Holland@astrazeneca.com
D000818:Animals; D016002:Discriminant Analysis; D051379:Mice; D010336:Pathology / Q000379:methods*; D051381:Rats; D018675:Toxicity Tests / Q000379:methods*; D014116:Toxicology / Q000379:methods*