A comparison of statistical approaches used to evaluate change in cognitive function following pharmacologic challenge: an example with lorazepam.
BACKGROUND
Neuropsychological tests are commonly used in psychopharmacological research to understand the nature and the magnitude of cognitive effects of licensed and novel compounds. While the science of cognitive change assessment has advanced considerably, statistical techniques used to guide inferences about differences in cognitive change have not been considered in the same detail, especially in light of recent advances in modeling repeated data.


METHODS
Data from a randomized, placebo-controlled, crossover study of the effect of an acute dose of lorazepam on cognitive function in healthy adults were analyzed using five statistical approaches (paired sample t-test, area under curve (AUC), repeated measures analysis of variance (ANOVA), change from baseline, and linear mixed models (LMM)). Results of significance tests and effect sizes were compared at maximum concentration (C(max)) and over the ascending slopes of cognitive performance.


RESULTS
LMM approaches were superior to other statistical approaches with respect to results of significance testing and magnitudes of estimated effect size change.


CONCLUSIONS
Results of this study suggest that employment of LMM, which permit examination of specific fixed effects (e.g., time, treatment, treatment x time) and that are not confounded by between-subject variability, provide a sensitive approach to detecting the cognitive effects of pharmacologic challenges, even with small samples.
Pietrzak
Robert H
RH
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06516, USA. robert.pietrzak@yale.edu
Fredrickson
Amy
A
Snyder
Peter J
PJ
Maruff
Paul
P
D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D002490:Central Nervous System / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003198:Computer Simulation; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D016014:Linear Models; D008140:Lorazepam / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged
D006993:Hypnotics and Sedatives; D008140:Lorazepam