The Development of Study Exit Criteria for Evaluating Antimanic Compounds
J Clin Psychiatry 2001;62:421-425
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: There is increasing interest
on the part of investigators and the public at large in finding
ways to study and improve treatments for the seriously mentally
ill without exposing such individuals to unnecessary risks. One
group of particular interest in this regard are patients
suffering from acute mania. We set out to define "exit"
criteria or novel clinical endpoints that might help to assess
the efficacy of antimanic compounds. We sought a method that
would be safer, more economical, and less sensitive to
nonspecific factors in the clinical environment while still
allowing unambiguous assessment of efficacy.
Method: From a pool of subjects being screened
for or already participating in intervention studies, we
retrospectively identified 76 admissions of patients with a manic
or mixed episode according to DSM-IV. We fit a mixed-effects
regression model to all available data obtained using the
Bech-Rafaelsen Mania Scale from admission to day 28 of treatment.
Using the estimated model coefficients, we obtained empirical
Bayes (EB) estimates of each subject's trend coefficients based
on (1) all available data and (2) data through day 11 of
treatment for mania.
Results: We found a high correlation (r =
.67) between EB estimates of final response at day 28 and actual
day 28 scores on the Bech-Rafaelsen scale based on scores through
day 11. When subjects were categorized as full, partial, or
nonresponders according to their final Bech-Rafaelsen score, we
were able to show that only 2 of the 23 predicted nonresponders
became full responders, 27 of the 31 predicted full responders
became full responders, and 16 of the 22 predicted partial
responders became partial or full responders.
Conclusion: We conclude on the basis of this
chart review study that it should be possible to define exit
criteria for trials assessing the efficacy of antimanic compounds
on the basis of relatively short duration exposure to