On April 23, 2004, a joint meeting of the FDA, NIMH, MATRICS investigators, and experts from academia and the pharmaceutical industry was convened to develop guidelines for the design of clinical trials of cognitive-enhancing drugs for neurocognitive impairments in patients with schizophrenia.
Experts were asked to address specific questions relating to clinical trial design of adjunctive/co-treatment and broad spectrum agents. At the workshop, experts reviewed relevant evidence before offering the discussion panel proposed guidelines for a given subset of questions. The discussion panel, which consisted of presenters and representatives from FDA, NIMH, academia, and industry, deliberated to reach consensus on suggested guidelines. When evidence was insufficient, suggested guidelines represent the opinion of a cross-section of the presenters and discussion panel.
Guidelines were developed for inclusion criteria, the use of co-primary outcome measures, and statistical approaches for study design. Consensus was achieved regarding diagnostic and concomitant medication inclusion criteria and on the use of cognitive screening measures. A key guideline was to limit the trial to patients in the residual phase of their illness, who have a predefined level of positive, negative, and affective symptoms. The most difficult issues were the feasibility of including a co-primary measure of functional improvement and the choice of comparator agent for a trial of a broad spectrum agent (with antipsychotic and cognitive-enhancing effects).
The suggested guidelines represent reasonable starting points for trial design of cognitive-enhancing drugs, with the understanding that new data, subsequent findings, or other methodological considerations may lead to future modifications.
"To examine transfer to untrained tasks the MATRICS Consensus Cognitive Battery (MCCB; Nuechterlein et al., 2008) and Cogstate (Westerman et al., 2001) were administered before and after the ten cognitive training sessions. Two baseline measures were taken (B1 and B2) in line with clinical trial recommendations done to reduce variance due to task unfamiliarity (Buchanan et al., 2005). "
"(2015), http://dx.doi.org/10.1016/j.scog.2014.12.002 patients (Mausbach et al., 2008). UPSA has been recommended as a coprimary assessment of cognition in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Project (Buchanan et al., 2005), in line with its potential sensitivity to change (Leifker et al., 2010). Currently, several clinical trials employ improvements in UPSA scores as one of the outcomes when evaluating a possible " cognitive-enhancing " drug or remediation. "
[Show abstract][Hide abstract] ABSTRACT: The UCSD Performance-based Skills Assessment (UPSA) is a measure of Functional Capacity and assesses skills involved in community tasks. It has good psychometrics properties, and is currently recommended as a co-primary assessment of cognition in the MATRICS Project. To our knowledge so far, there are no studies in western developing countries concerning Functional Capacity in Schizophrenia. The aims of this study were to translate, culturally adapt and validate the UPSA to assess Functional Capacity in community-dwelling patients with Schizophrenia living in Brazil. Eighty-two subjects (52 patients, 30 controls) were evaluated using: the Brazilian version of the UPSA (UPSA-1-BR), PANSS, Personal and Social Performance (PSP) and Global Assessment of Functioning (GAF). In the reliability test, UPSA-1-BR showed good Internal Consistency (Cronbach’s alpha of 0.88) and strong correlation between test and retest (4-month gap; r = 0.91; p < 0.01). Spearman’s rho values showed a moderate correlation between UPSA-1-BR and both PSP (0.50; p < 0.01) and GAF (0.46; p < 0.01) scores. UPSA-1-BR is capable of differentiating people with and without Schizophrenia. Patients scored lower than controls (58.9 versus 79.1), with an AUC of 0.79 (95%IC: 0.69–0.89). Sensitivity and specificity values of 0.71 and 0.70, respectively, were found in the cut-off point of 73.5, for separation of patients and controls, with predictive values of 80% (positive) and 58% (negative). UPSA-B-BR was also evaluated. UPSA-1-BR and its brief version presented adequate psychometric properties and proved to be valid and reliable instruments in the assessment of Functional Capacity in subjects with Schizophrenia.
"In recent years interest in the relationship between cognitive and functional impairments in patients with schizophrenia has grown (Green et al., 2000). Abundant evidence suggests that cognitive deficits are important determinants of impairments in most functional domains and are targeted for treatment in schizophrenia (Buchanan et al., 2005). Cognitive impairments have been shown to exert a general influence on functioning (Evans et al., 2003), with minimal evidence of differential correlations with different functional domains. "
[Show abstract][Hide abstract] ABSTRACT: Previously institutionalized older patients with schizophrenia show changes in cognitive and functional capacity over time. This study examined changes in real-world functioning in a sample of people with schizophrenia who varied in their history of long-term institutionalization and related changes in real world functioning to changes in cognition and functional capacity over the follow-up period.
Older patients with schizophrenia (n = 111) were examined with assessments of cognitive functioning, functional capacity, clinical symptoms, and everyday functioning. They were then followed up to 45 months and examined up to two times. Mixed-model regression was used to examine changes in real-world functioning in social, everyday living, and vocational domains over the follow-up period and identify potential predictors of change.
Everyday functioning worsened over time in all three domains. Although length of longest hospitalization predicted worsening, this influence was eliminated when the course of functional capacity was used to predict the course of everyday functioning. For both vocational and everyday living domains, as well as the composite score on functional status, worsening in performance based measures of everyday functioning and social competence predicted worsening in real world functioning. Changes in negative symptoms further predicted worsening in the everyday living domain.
Worsening in everyday functioning is found in people with schizophrenia and those with a history of greater chronicity and severity of illness seem more affected. These influences seem to be expressed through worsening in the ability to perform everyday functional skills. Potential causes of these changes and implications for reducing these impairments are discussed.
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