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IMPROVING SIGNAL DETECTION IN SCHIZOPHRENIA CLINICAL TRIALS
138
Abstracts
IMPROVING SIGNAL DETECTION IN SCHIZOPHRENIA CLINICAL TRIALS Michael Detke MedAvante Research Institute, and the Departments of Psychiatry, Indiana University School of Medicine & Harvard Medical School Hamilton, NJ, USA 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.
in Schizophrenia (MATRICS) initiative, which helpfully characterised the cognitive deficits associated with schizophrenia. The MATRICS group also suggested the use of tests from clinical psychology as a means of assessing these key cognitive domains. Other groups have also proposed measures of the MATRICS specified domains. In this presentation we will consider data from trials that have employed the MATRICS Consensus Cognitive Battery (MCCB) as well as those to have employed other cognitive measures. We will also give consideration to the issue of the clinical relevance of cognitive effects and the relationship between cognitive and functional improvement. doi:10.1016/j.schres.2010.02.108
FUNCTIONAL OUTCOME AS A LONG-TERM TREATMENT GOAL: DEFINITION AND ASSESSMENT IN CLINICAL TRIALS Nina Schooler Departments of Psychiatry & Behavioral Sciences, SUNY Downstate Medical Center, and The Zucker Hillside Hospital Brooklyn, NY, USA Functional outcome as a long-term treatment goal: definition and assessment in clinical trials. As clinical trials in schizophrenia become longer and targets for treatment become more specific, the concern with outcomes has developed beyond domains that are readily assessed by clinical observers and direct trial participant report. In particular, the current focus on cognitive deficits in schizophrenia has led to increased interest in functional outcomes that are mediated in part by cognitive deficits. This presentation will review the current state of functional outcome assessment from a number of critical perspectives: burden, opportunity to observe, availability of assessor and validity of assessment. Most prior consideration of instruments has involved scale or instrument level comparisons. The focus here will be on the examination of domains of functional outcome such as work, family relationships, social relationships, living situation and life orientation/satisfaction to identify optimal strategies for assessment that are domain specific. Consideration of domain specificity may be advantageous in encouraging development of instruments that will facilitate evaluation of new treatments. doi:10.1016/j.schres.2010.02.109
doi:10.1016/j.schres.2010.02.107
John Harrison Division of Neurosciences and Mental Health, Imperial College, and CogState Ltd. London United Kingdom
Symposium 19 AUTISTIC AND COGNITIVE TRAITS IN THE GENETIC UNDERSTANDING OF THE CONTINUUM IN NEURODEVELOPMENTAL DISORDERS AND FUNCTIONAL PSYCHOSIS Co-Chairpersons: Lourdes Fañanás, Marie-Odile Krebs Tuesday, 13 April, 2010 - 3:30 pm - 5:30 pm
Measuring the mind: Assessing the cognitive effects of new compounds for the treatment of schizophrenia There has been considerable recent interest in seeking to develop drugs to rescue cognition in patients with schizophrenia. The academic, pharmaceutical and test development communities have responded to the need for standardized measures of cognitive change for use in studies of Cognitive Impairment Associated with Schizophrenia (CIAS) in a variety of ways. A major impetus was provided by the Measurement and Treatment Research to Improve Cognition
Overall Abstract: The assumption that neuropsychiatric disorders are phenotypically heterogeneous with overlapping findings suggests the participation of more than one etiological factor and pathophysiological process, some of them being partly shared across the traditional classification categories. Autistic Spectrum Disorders and Psychotic Disorders are complex neuropsychiatric syndromes affecting between 0.3 and 0.6% of the children and 3% of the adult world population (1, 2). Although their separation is clear since DSM-
MEASURING THE MIND: ASSESSING THE COGNITIVE EFFECTS OF NEW COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA
Abstracts
IMPROVING SIGNAL DETECTION IN SCHIZOPHRENIA CLINICAL TRIALS Michael Detke MedAvante Research Institute, and the Departments of Psychiatry, Indiana University School of Medicine & Harvard Medical School Hamilton, NJ, USA 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.
in Schizophrenia (MATRICS) initiative, which helpfully characterised the cognitive deficits associated with schizophrenia. The MATRICS group also suggested the use of tests from clinical psychology as a means of assessing these key cognitive domains. Other groups have also proposed measures of the MATRICS specified domains. In this presentation we will consider data from trials that have employed the MATRICS Consensus Cognitive Battery (MCCB) as well as those to have employed other cognitive measures. We will also give consideration to the issue of the clinical relevance of cognitive effects and the relationship between cognitive and functional improvement. doi:10.1016/j.schres.2010.02.108
FUNCTIONAL OUTCOME AS A LONG-TERM TREATMENT GOAL: DEFINITION AND ASSESSMENT IN CLINICAL TRIALS Nina Schooler Departments of Psychiatry & Behavioral Sciences, SUNY Downstate Medical Center, and The Zucker Hillside Hospital Brooklyn, NY, USA Functional outcome as a long-term treatment goal: definition and assessment in clinical trials. As clinical trials in schizophrenia become longer and targets for treatment become more specific, the concern with outcomes has developed beyond domains that are readily assessed by clinical observers and direct trial participant report. In particular, the current focus on cognitive deficits in schizophrenia has led to increased interest in functional outcomes that are mediated in part by cognitive deficits. This presentation will review the current state of functional outcome assessment from a number of critical perspectives: burden, opportunity to observe, availability of assessor and validity of assessment. Most prior consideration of instruments has involved scale or instrument level comparisons. The focus here will be on the examination of domains of functional outcome such as work, family relationships, social relationships, living situation and life orientation/satisfaction to identify optimal strategies for assessment that are domain specific. Consideration of domain specificity may be advantageous in encouraging development of instruments that will facilitate evaluation of new treatments. doi:10.1016/j.schres.2010.02.109
doi:10.1016/j.schres.2010.02.107
John Harrison Division of Neurosciences and Mental Health, Imperial College, and CogState Ltd. London United Kingdom
Symposium 19 AUTISTIC AND COGNITIVE TRAITS IN THE GENETIC UNDERSTANDING OF THE CONTINUUM IN NEURODEVELOPMENTAL DISORDERS AND FUNCTIONAL PSYCHOSIS Co-Chairpersons: Lourdes Fañanás, Marie-Odile Krebs Tuesday, 13 April, 2010 - 3:30 pm - 5:30 pm
Measuring the mind: Assessing the cognitive effects of new compounds for the treatment of schizophrenia There has been considerable recent interest in seeking to develop drugs to rescue cognition in patients with schizophrenia. The academic, pharmaceutical and test development communities have responded to the need for standardized measures of cognitive change for use in studies of Cognitive Impairment Associated with Schizophrenia (CIAS) in a variety of ways. A major impetus was provided by the Measurement and Treatment Research to Improve Cognition
Overall Abstract: The assumption that neuropsychiatric disorders are phenotypically heterogeneous with overlapping findings suggests the participation of more than one etiological factor and pathophysiological process, some of them being partly shared across the traditional classification categories. Autistic Spectrum Disorders and Psychotic Disorders are complex neuropsychiatric syndromes affecting between 0.3 and 0.6% of the children and 3% of the adult world population (1, 2). Although their separation is clear since DSM-
MEASURING THE MIND: ASSESSING THE COGNITIVE EFFECTS OF NEW COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA