Informatics tools to improve clinical research.

During the conduct of complex clinical trials, there are numerous sources and types of data collection and project coordination problems. Methods and approaches to address the conduct of a trial vary in both the cost and time to perform and the potential benefit. Informatics tools can help trial coordinators and investigators ensure the collection of high quality research data during all phases of a clinical trial.

Does the manic/mixed episode distinction in bipolar disorder patients run true over time?

OBJECTIVE: The authors sought to determine whether the manic/mixed episode distinction in patients with bipolar disorder runs true over time. METHOD: Over an 11-year period, the observed distribution of manic and mixed episodes (N=1,224) for patients with three or more entries in the management information system of a community mental health center (N=241) was compared to the expected distribution determined by averaging 1,000 randomly generated simulations. RESULTS: Episodes were consistent (all manic or all mixed) in significantly more patients than would be expected by chance. CONCLUSIONS: These data suggest a pattern of diagnostic stability over time for manic and mixed episodes in patients with bipolar disorder. Careful prospective studies of this issue are needed.

Effects of the CCK(B) antagonist CI-988 on responses to mCPP in generalized anxiety disorder.

In order to evaluate the effect of the CCK(B) antagonist CI-988 on behavioral, neuroendocrine, and physiologic responses to the mixed, post-synaptic serotonin (5-HT) agonist/antagonist mCPP, 16 patients with a principal DSM-III-R diagnosis of generalized anxiety disorder (GAD) were enrolled in a study that involved two challenge tests. On one day, patients received a single oral dose of CI-988 followed 30 min later by an i.v. infusion of 0.1 mg/kg mCPP. On a second test day patients received placebo CI-988 followed 30 min later by active i.v. mCPP. The sequence of CI-988 was randomly assigned and the testing was conducted in double-blind fashion. In an initial dose-finding phase (N = 6) with a dose of CI-988 of 25 mg, there were no significant between-test differences in behavioral response to mCPP. Accordingly, the second phase of the study was conducted with a CI-988 dose of 100 mg in another of patients (N = 10). CI-988 (100 mg) was well tolerated and had no significant effects on pretest anticipatory anxiety. There was no significant blunting of the anxiety response to mCPP as a result of CI-988 administration, nor did CI-988 affect physiologic or neuroendocrine measures. Correlations between peak changes in plasma levels of CI-988 and mCPP-induced anxiety in the high-dose patient group were not significant. Overall, these findings did not provide evidence of anxiolytic effects of CI-988 in patients with GAD. The lack of effect of CI-988 on neuroendocrine and physiological measures further suggests that CI-988's pharmacological effects could be independent of 5-HT function. However, follow-up studies using higher doses of CI-988 are indicated to confirm this preliminary finding as are studies more closely evaluating the interrelationship between CCK and 5-HT function in GAD.

Pretreatment patient factors predicting attrition from a multicenter randomized controlled treatment study for panic disorder.

This study examined pretreatment factors associated with attrition from a clinical trial for panic disorder. The study group consisted of 162 patients who began 11-visit treatments. Six domains (demography, panic disorder severity, psychiatric comorbidity, illness/treatment attributions, coping styles, and personality styles) with 52 variables were used to predict attrition. One hundred twenty-two patients completed and 40 dropped out from treatment. Final multivariate regression analyses showed that the following two variables were independently associated with attrition: lower household income and negative treatment attitudes; attributing the panic disorder to life stressors and greater age were independently associated with attrition at the trend level. Preliminary analyses suggested, in addition, associations between attrition and lower education, shorter length of prior treatment, higher anxiety sensitivity, lower agoraphobic avoidance, and a coping style of seeking social support that were not confirmed by best predictor analysis. Psychiatric comorbidity and personality styles were unrelated to attrition. The implications of these findings for future research and clinical practice are discussed.

Multicenter collaborative panic disorder severity scale.

OBJECTIVE: To address the lack of a simple and standardized instrument to assess overall panic disorder severity, the authors developed a scale for the measurement of panic disorder severity. METHOD: Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder (with no or mild agoraphobia) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder. In addition, 89 of these patients were reevaluated with the same scale after short-term treatment. A subset of 24 patients underwent two independent assessments to establish interrater reliability. Internal consistency, convergent and discriminant validity, and sensitivity to change were also determined. RESULTS: The Panic Disorder Severity Scale was associated with excellent interrater reliability, moderate internal consistency, and favorable levels of validity and sensitivity to change. Individual items showed good convergent and discriminant validity. Analysis suggested a two-factor model fit the data best. CONCLUSIONS: The Panic Disorder Severity Scale is a simple, efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder. However, further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed.