As I recently reviewed a set of interim data with one of my students, we both remarked at how underwhelming the data set appeared even though it amounted to weeks of work and several dozens of mice. It is sometimes striking how pharmacological evaluations, which require close to 50 animals to attain statistical power in dose-response evaluations, can seem unimpressive. The data from many different animals is compressed into a median value based off a statistical regression using the Probit model, but each data point on the statistical regression requires n’s of at minimum 8 individuals for adequate statistical power. This allows us to calculate a median effective dose, or ED50. An ED50 may not look like a lot of work, but it is!
So, when we publish a comprehensive dataset of ED50s and median behaviorally-impairing doses (or TD50 for short), it can represent years of work. The NINDS even has a resourceful database of over 40 years of ED50/TD50 calculations that demonstrates how much time, effort, and money can go into defining the proper dose and time of drug administration necessary to demonstrate anticonvulsant efficacy. Our lab has now published a comparative pharmacology study in both inbred (C57BL/6) and outbred (CF-1) mouse lines. The use of both outbred and inbred mouse lines provides a robust comparison to genetically similar and dissimilar individuals, which is very useful for human treatment. This project demonstrates how much time goes into drug discovery – our lab book records for this effort date back to 2016! And yet, the tables are simple.
I hope you will find this effort useful for your drug screening!