MEASURING THE MIND: ASSESSING THE COGNITIVE EFFECTS OF NEW COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA

Abstract

Improving Signal Detection in Schizophrenia Clinical Trials – Centralized Ratings / Centralized Review. Clinical trials in schizophrenia fail more frequently than they should and the drug-placebo separation has been worsening. This presentation will focus on two possible root causes: first, some patients enrolled into clinical trials may be inaccurately diagnosed and/or insufficiently ill to benefit from the treatments being tested; and second, assessment methods for detecting efficacy may be inadequate and/or inconsistent. The first potential root cause is patient ascertainment. Previous studies in MDD & GAD have shown that 1/3 to 1/2 of the patients enrolled in trials by site raters would be excluded based on the patient's self-rating or remote blinded clinicians' ratings of initial severity. New data from ongoing schizophrenia studies shows that 5-56% of patients enrolled in trials by site raters would be excluded based on remote blinded clinicians' ratings of initial severity. New data on diagnosis at study entry in ongoing psychiatric trials show that an additional cohort of patients would be excluded with remote blinded clinicians performing the diagnostic evaluations. The second potential root cause is inadequate or inconsistent assessments. Data will be reviewed showing that >50% of assessments of primary efficacy scales were inadequately performed in one study, and that assessment quality decayed over the life of another trial. One potential solution to both of these possible root causes is to employ remote blinded clinicians to do assessments of key inclusion/exclusion criteria, such as diagnosis and initial severity, as well as to assess key outcomes. Data will be reviewed showing that this methodology improved signal detection in a recent schizophrenia clinical trial. An alternative to centralized assessments by videoconference is to videotape assessments performed at clinical trial sites, for review by a continuously calibrated group of centralized clinicians, much as a single cardiologist reviews EKGs from multiple sites. Initial data from this approach will be presented, with trends showing improvement in diagnostic and outcomes assessments from clinical trials in various psychiatric indications.