RT Journal Article
SR Electronic
T1 Balancing sensitivity and specificity in preclinical research
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.17.476585
DO 10.1101/2022.01.17.476585
A1 Meggie Danziger
A1 Ulrich Dirnagl
A1 Ulf Toelch
YR 2022
UL http://biorxiv.org/content/early/2022/04/19/2022.01.17.476585.abstract
AB The success of scientific discovery in preclinical drug development is based on the different roles of exploration and confirmation. Exploration requires sensitivity while confirmation needs to be specific. Based on published empirical data, we simulated two preclinical research trajectories to examine their effectiveness to detect true effects while keeping animal numbers low. We compare a conventional p-value based approach with a method based on an a priori determined smallest effect size of interest (SESOI). Using a SESOI increases transition rates from exploration to confirmation and results in higher detection rates across the trajectory. Specificity in the SESOI trajectory increases if the prior probability of true effects is low. We conclude that employing a SESOI is superior to a p-value based approach. Based on our findings, we propose a reconsideration of planning and conducting preclinical experiments, especially when the prior probability of true hypotheses is low.Competing Interest StatementThe authors have declared no competing interest.