Joint modeling of performance and subjective reporting to assess sensitivity to drug-induced sleepiness.
In an NASA ground study, two forms of cognitive tests were evaluated in terms of their sensitivity to sleepiness induced by the drug promethazine (PMZ). Performance for the two test modes (Y(1) and Y(2)), PMZ concentration, and a self-reported sleepiness using the Karolinska Sleepiness Scale (KSS) were monitored for 12 h post dose. A problem arises when using KSS to establish an association between true sleepiness and performance because KSS scores are discrete and also because they tend to concentrate on certain values. Therefore, we define a latent sleepiness measure X as an unobserved continuous random variable describing a subject's actual state of sleepiness. Under the assumption that drug concentration affects X, which then affects Y(1), Y(2), and KSS, we use Bayesian methods to estimate joint equations that permit unbiased comparison of the performance measures' sensitivity to X. The equations incorporate subject random effects and include a negativity constraint on subject-specific slopes of performance with respect to sleepiness.
Fiedler
James
J
National Space Biomedical Research Institute, One Baylor Plaza, NA-425, Houston, TX 77030, U.S.A.
Feiveson
Alan H
AH
Hayat
Matthew J
MJ
Vaksman
Zalman
Z
Boyd
Jason L
JL
Putcha
Lakshmi
L
D000465:Algorithms; D001499:Bayes Theorem; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D059026:Diagnostic Self Evaluation; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced* / Q000175:diagnosis*; D006801:Humans; D008390:Markov Chains; D008568:Memory / Q000187:drug effects / Q000502:physiology; D015233:Models, Statistical; D009010:Monte Carlo Method; D009483:Neuropsychological Tests; D017711:Nonlinear Dynamics; D011398:Promethazine / Q000009:adverse effects* / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D012894:Sleep Stages / Q000187:drug effects; D012984:Software; D018489:Space Motion Sickness / Q000517:prevention & control
D011398:Promethazine