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Chronic Schizophrenia (chronic + schizophrenia)
Selected AbstractsPrevalence and relationship to delusions and hallucinations of anxiety disorders in schizophreniaDEPRESSION AND ANXIETY, Issue 2 2003F.R.C.P.C., Philip Tibbo M.D. Abstract We investigated the prevalence of anxiety disorders in a sample of individuals with chronic schizophrenia, controlling for anxiety symptoms that may be related to delusions and hallucinations, and the possible differences in clinical variables between the groups. Individuals with a diagnosis of schizophrenia and able to give informed consent were recruited from the community. The Mini International Neuropsychiatric Interview (MINI) was administered to both confirm the DSM-IV diagnosis of schizophrenia and screen for comorbid anxiety disorders. If a comorbid anxiety disorder was found, its relation to the individual's delusions and hallucinations was examined. Clinical rating scales for schizophrenia were administered as well as rating scales for specific anxiety disorders where appropriate. Overall, anxiety disorders ranged from 0% [ for Post Traumatic Stress Disorder (PTSD)] to 26.7% [ for generalized anxiety disorder (GAD) and agoraphobia without panic] with lower rates when controlled for anxiety symptoms related to delusions and hallucinations. In investigating clinical variables, the cohort was initially divided into schizophrenics with no anxiety disorders and those with an anxiety disorder; with further analyses including schizophrenics with anxiety disorders related to delusions and hallucinations and those with anxiety disorders not related to delusions and hallucinations. The most consistent difference between all the groups was on the PANSS-G subscale. No significant differences were found on the remaining clinical variables. Comorbid anxiety disorders in schizophrenia can be related to the individual's delusions and hallucinations, though anxiety disorders can occur exclusive of these positive symptoms. Clinicians must be aware that this comorbidity exists in order to optimize an individual's treatment. Depression and Anxiety 17:65,72, 2003. © 2003 Wiley-Liss, Inc. [source] An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2006D. C. Henderson Objective:, We conducted this 6-week open-label trial to examine the effects of adjunctive aripiprazole in clozapine-treated subjects on weight, lipid and glucose metabolism, as well as positive and negative symptoms of schizophrenia. Method:, Ten clozapine-treated subjects received aripiprazole augmentation; eight completed the 6-week trial and two ended at week 4. Eighty percent were male, the mean age was 38.7 ± 8.9 years and the mean clozapine dose was 455 ± 83 mg daily. Results:, There was a significant decrease in weight (P = 0.003), body mass index (P = 0.004), fasting total serum cholesterol (P = 0.002) and total triglycerides (P = 0.04) comparing baseline to study endpoint. There was no significant change in total Positive and Negative Syndrome Scale scores. Conclusion:, This combination may be useful for clozapine-associated medical morbidity and must be studied in placebo-controlled double-blind randomized trials to determine efficacy and safety. [source] Neuroleptic malignant syndrome during olanzapine and levomepromazine treatmentACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2000K. Järventausta Objective: To date only five reports of neuroleptic malignant syndrome (NMS) related to olanzapine exist. The first case report was published in November 1998. Method: We report the case of a 78-year-old woman suffering from chronic schizophrenia who developed a NMS while being treated with olanzapine and levomepromazine. Before this her medication had been unchanged for more than 2 years. Results: When treated with olanzapine and levomepromazine, the patient had a fulminant NMS which was complicated with pneumonia. When the neuroleptic drug treatment was discontinued, the patient recovered. However, when this combination was restarted later due to severe agitation and hallucinations, the symptoms of NMS reappeared. Conclusion: This case report shows that the neuroleptic malignant syndrome can occur during olanzapine treatment as well as during treatment with conventional neuroleptics. This syndrome may develop even after a long and stable neuroleptic treatment. [source] Amisulpride: a review of its efficacyin schizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 400 2000H. J. Möller Objective: To assess the efficacy of the new atypical antipsychotic drug, amisulpride. Method: Studies comparing the efficacy of amisulpride with that of haloperidol and risperidone, respectively, are reviewed. Outcome measures were Clinical Global Impression, Brief Psychiatric Rating Scale (BPRS), and Positive And Negative Symptom Scale (PANSS) scores. Results: Amisulpride was at least as effective as haloperidol and risperidone in the improvement of positive symptoms, and significantly more efficacious than haloperidol in reducing PANSS negative subscores (P=0.038) in patients with acute exacerbations. Amisulpride demonstrated a greater improvement in BPRS total scores (P<0.05) and PANSS negative subscores (P=0.0001) than haloperidol after 12 months of treatment in chronic schizophrenic patients with acute exacerbations. Conclusion: Amisulpride can thus be considered for use as first-line treatment of acute and chronic schizophrenia. [source] Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism influencing glycogen synthase kinase 3-, activityGENES, BRAIN AND BEHAVIOR, Issue 4 2010F. Benedetti At the crossroad of multiple pathways regulating trophism and metabolism, glycogen synthase kinase (GSK)3 is considered a key factor in influencing the susceptibility of neurons to harmful stimuli (neuronal resilience) and is a target for several psychiatric drugs that directly inhibit it or increase its inhibitory phosphorylation. Inhibition of GSK3 prevents apoptosis and could protect against the neuropathological processes associated with psychiatric disorders. A GSK3- ,promoter single-nucleotide polymorphism (rs334558) influences transcriptional strength, and the less active form was associated with less detrimental clinical features of mood disorders. Here we studied the effect of rs334558 on grey matter volumes (voxel-based morphometry) of 57 patients affected by chronic schizophrenia. Carriers of the less active C allele variant showed significantly higher brain volumes in an area encompassing posterior regions of right middle and superior temporal gyrus, within the boundaries of Brodmann area 21. The temporal lobe is the brain parenchymal region with the most consistently documented morphometric abnormalities in schizophrenia, and neuropathological processes in these regions develop soon at the beginning of the illness. These results support the interest for GSK3- ,as a factor affecting neuropathology in major behavioural disorders, such as schizophrenia, and thus as a possible target for treatment. [source] A single application of MK801 causes symptoms of acute psychosis, deficits in spatial memory, and impairment of synaptic plasticity in ratsHIPPOCAMPUS, Issue 2 2008Denise Manahan-Vaughan Abstract Schizophrenia is mostly a progressive psychiatric illness. Although cognitive changes in chronic schizophrenia have been investigated, little is known about the consequences of a single psychotic episode on memory mechanisms and formation. We investigated changes in hippocampal long-term potentiation (LTP) and spatial memory in a rat model of an acute psychotic episode. Application of NMDA receptor antagonists, such as MK801 (dizolcilpine) in rats, have been shown to give rise to an acute and short-lasting behavioral state, which mirrors many symptoms of schizophrenia. Furthermore, NMDA antagonist-intake in humans elicits symptoms of schizophrenia such as hallucinations, delusions, and affective blunting. We therefore treated animals with a single systemic injection of MK801 (5 mg/kg). Increased stereotypy, locomotion, and ataxia were evident immediately after MK801-treatment, with effects disappearing within 24 h. MK801-treatment caused a disruption of prepulse inhibition of the acoustic startle reflex, 1 day but not 7 or 28 days after treatment. These effects were consistent with the occurrence of an acute psychotic episode. LTP was profoundly impaired in freely moving rats 7 days after MK801 application. Four weeks after treatment, a slight recovery of LTP was seen, however marked deficits in long-term spatial memory were evident. These data suggest that treatment with MK801 to generate an acute psychotic episode in rats, gives rise to grave disturbances in synaptic plasticity and is associated with lasting impairments with the ability to form spatial memory. © 2007 Wiley-Liss, Inc. [source] Stability of cognitive impairment in chronic schizophrenia over brief and intermediate re-test intervalsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2009Robert H. Pietrzak Abstract Objective This study examined between- and within-subject stability of cognitive performance in individuals with chronic schizophrenia. Methods Thirty individuals with schizophrenia and 20 healthy controls matched by age, sex, education, and estimated IQ underwent repeated cognitive assessments at baseline and 30 days using computerized tests of psychomotor function, visual attention/information processing, non-verbal learning, and executive function. Results Compared to healthy controls, individuals with schizophrenia scored lower on all cognitive measures and demonstrated greater variability in cognitive performance. Within-subject variability in cognitive performance in both the schizophrenia and healthy control groups remained stable at brief (i.e., hours) and intermediate (i.e., one month) assessments. Conclusions These results demonstrate the stability of between- and within-subject variability in cognitive performance in schizophrenia, and suggest that variability in cognitive performance may reflect an inherent characteristic of the disorder, rather than differences in test,retest reliability/error of cognitive measures. Copyright © 2008 John Wiley & Sons, Ltd. [source] Retrospective database analysis on the effectiveness of typical and atypical antipsychotic drugs in an outpatient clinic settingHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2007Cengiz Akkaya Abstract Objective To report the outcomes of a retrospective database analysis to compare the effectiveness of atypical and typical antipsychotic drugs. Methods Medical records of patients admitted to the psychiatry outpatient clinic between January 1998 and October 2005 were retrospectively reviewed. Data obtained from patient records were noted on a special form assessing four aspects of the treatment history: socio-demographic features, disease characteristics, initial treatment at the time of admission, and course of treatment. Patient groups (typical/atypical and Risperidone/Haloperidol/Olanzapine) were compared for time to all-cause medication discontinuation and rate of discontinuation. Results There was no statistically significant difference in the duration of treatment between patients using atypical (n,=,150) and typical (n,=,124) antipsychotics. The duration of treatment was significantly longer in patients on Haloperidol (n,=,91) compared with those on Risperidone (n,=,63). Rates of discontinuation over 18 months were 59.3% for patients on atypical antipsychotics and 57.3% for those on typical antipsychotics, and 68.3% for patients on Risperidone, 51.6% for patients on Haloperidol and 54.3% for patients on Olanzapine. Conclusion Despite our hypothesis patients with chronic schizophrenia discontinued their atypical and typical antipsychotics, at a high rate with no significant difference indicating substantial limitations in the effectiveness of these drugs. Copyright © 2007 John Wiley & Sons, Ltd. [source] Plasma serotonin response to carbohydrate-rich food in chronic schizophrenic patients: clozapine versus classic antipsychotic agentsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2001Yaffa Vered Abstract Researchers have reported a stimulatory effect of carbohydrate-rich intake on platelet-poor plasma (PPP) serotonin (5-HT) levels in healthy human subjects. Dietary manipulation may serve as a safer and less invasive means than pharmacologic challenge to provoke serotonergic responsivity in studies of schizophrenia. In the present study, we used the carbohydrate-rich meal test as an indicator of 5-HT activity in 12 patients with chronic schizophrenia maintained for at least 6 months on clozapine. PPP 5-HT levels were measured at baseline and at 1, 2 and 3,h after administration of the test. Findings were compared with those in schizophrenic patients treated with classic antipsychotic agents for the same duration. The maximal PPP 5-HT response was reached 120 min after meal administration in the clozapine-treated group and 60 min after in the classic antipsychotic-treated group (P<0.05 vs baseline for both). The 5-HT level (as percentage of baseline) at 60 min was significantly lower in the clozapine-treated group (P<0.02), as were individual PPP 5-HT peak values (P<0.05). The individual time to reach the peak response was similar in the two groups. Our results indicate that in patients with chronic schizophrenia 5-HT responsivity to the natural challenge of carbohydrate-rich meals is lower in those treated with clozapine than in those given classic antipsychotic agents. Values in both groups were lower than those in an appropriate historical comparative group of healthy subjects. We suggest that both clozapine and classic antipsychotic agents suppress serotonergic system sensitivity, but to a different degree. Copyright © 2001 John Wiley & Sons, Ltd. [source] Comparison of the metabolic and economic consequences of long-term treatment of schizophrenia using ziprasidone, olanzapine, quetiapine and risperidone in Canada: a cost-effectiveness analysisJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 4 2010Roger S. McIntyre MD FRCPC Abstract Rationale, aims and objectives, Second-generation antipsychotic agents have varying propensities to cause weight gain, elevated lipid levels and associated long-term complications. This study evaluates the cost-effectiveness of four second-generation antipsychotic agents used in Canada for the treatment of schizophrenia (ziprasidone, olanzapine, quetiapine, risperidone) with a focus on their long-term metabolic consequences. Method, Using data from the Clinical Antipsychotic Trials of Intervention Effectiveness Study, a semi-Markov model was developed to predict the incidence and associated costs of type 2 diabetes, cardiovascular complications (e.g. angina, myocardial infarction, stroke, cardiovascular disease death), and acute psychiatric hospitalizations in patients with chronic schizophrenia treated over 5 years. Incremental costs per quality-adjusted life year (QALY) gained were calculated from the perspective of the Canadian provincial ministries of health. Scenario and probabilistic sensitivity analyses were performed. Results, The total average cost of treatment with ziprasidone was $25 301 versus $28 563 with olanzapine, $26 233 with quetiapine and $21 831 with risperidone. Ziprasidone had the lowest predicted number of type 2 diabetes cases and cardiovascular disease events, and the highest QALY gains. Patients receiving quetiapine had the highest predicted number of hospitalizations. Ziprasidone was less costly and resulted in more QALYs compared with olanzapine and quetiapine. Compared with risperidone, ziprasidone was more costly and had higher QALYs, with an incremental cost per QALY gained of $218 060. Conclusion, Compared with olanzapine and quetiapine, ziprasidone produced savings to the health care system. Although ziprasidone generated incremental expenditures versus risperidone, it resulted in more QALYs. Based on this analysis, ziprasidone treatment possesses cost and therapeutic advantages compared with olanzapine and quetiapine. [source] Relationship of psychopathological symptoms and cognitive function to subjective quality of life in patients with chronic schizophreniaPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2010Kenji Tomida md Aims:, The purpose of the present study was to examine the extent of the effects of psychopathological symptoms and cognitive function on quality of life (QOL) in patients with chronic schizophrenia. Methods:, Data were obtained using the Japanese Schizophrenia Quality of Life Scale (JSQLS), Positive and Negative Syndrome Scale (PANSS), Wisconsin Card-Sorting Test (WCST) Keio version, and Continuous Performance Test (CPT) for 52 schizophrenia patients. Results:, Stepwise regression analysis showed that PANSS depression/anxiety factors predicted JSQLS psychosocial conditions and motivation/energy, and that WCST Categories Achieved predicted JSQLS symptoms/side-effects. Conclusions:, Psychopathological symptoms and cognitive function affect subjective QOL in patients with schizophrenia. If the final goal is treatment that improves QOL in a manner that patients themselves are aware of, clinicians probably need to consider a treatment strategy that improves depression/anxiety symptom. [source] Application of Empowerment Scale to patients with schizophrenia: Japanese experiencePSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 6 2007SUMIE YAMADA ms Abstract Rogers et al. invented the Empowerment Scale, and conducted a factor analysis, which found five factors: self-esteem, power, activism, righteous anger and optimism. Hata et al. translated this scale into Japanese and named it Empowerment Scale-J. They found that the score of the righteous anger factor does not have a significant correlation with the overall score of the Empowerment Score-J. With the aim of clarifying the characteristics of the Empowerment Scale-J, the purpose of the present study was to assess the levels of empowerment in 72 Japanese patients with chronic schizophrenia using the scale, and examine the relationship between the results of the scale and the results of the following two batteries: Social Adjustment Scale II (SAS II), and Expanded Attributional Style Questionnaire (EASQ; a questionnaire to assess some aspects of attitude toward negative circumstances). Four results were obtained as follows. No significant correlation was found between the score of righteous anger factor and overall score. No significant correlation was found between the Empowerment Scale-J score and the degree of social adjustment. Significant correlations were found between some subscales of Empowerment Scale-J and the degree of social adjustments: self-esteem and optimism, but inverse correlations were obtained between the power factor and the righteous anger factor and the degree of social adjustment. Results for the EASQ showed that subjects with a higher righteous anger score have a tendency opposite to that of subjects with higher social adjustment. On the basis of these results it is suggested that behavior related to the righteous anger among Japanese persons with schizophrenia may have some negative influence on their social adaptation and that in applying Empowerment scale-J attention should be paid to the significance of the righteous anger factor. [source] Can personality traits help us explain disability in chronic schizophrenia?PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2006ANDRÉS HERRÁN md Abstract, Psychotic features have been considered the main determinant of psychosocial function in schizophrenia. However, other variables are likely to affect dysfunction in these patients. The authors' hypothesis is that personality traits in outpatients with chronic schizophrenia differ from traits found in the healthy population and may be associated with disability in this disorder. A total of 62 patients with schizophrenia were evaluated with the Eysenck Personality Questionnaire (EPQ) and the Tridimensional Personality Questionnaire (TPQ). Psychotic features were measured with the help of the Positive and Negative Syndrome Scale (PANSS). Disability was assessed with the Disability Assessment Schedule (DAS). A total of 43 healthy subjects were used as controls for personality measurements. Normative data for the study population was also used to evaluate results in patients. Patients with schizophrenia had higher levels of neuroticism (median in percentile 65) and lower levels of extraversion (median in percentile 25) than the healthy population. Results of the TPQ showed higher harm avoidance and lower reward dependence levels compared to the healthy population. After multiple regression tests, negative symptoms were the strongest predictor of disability in patients with schizophrenia. Neuroticism contributed independently to the DAS overall behavior and global judgement subscales scores (more negative symptoms and higher neuroticism resulted in worse functioning), but not to the social role subscale. Outpatients with chronic schizophrenia showed high levels of neuroticism, harm avoidance, and introversion. Neuroticism significantly contributes to the long-term deficits found in patients with schizophrenia. [source] Attentional dysfunction of chronic schizophrenia: No association with long-term institutionalizationPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2002LUIGI CREMASCO MD Abstract Attentional processes play a central role in information selection, which is impaired in schizophrenic patients. In the present study, we attempted to characterize the attentional performance of chronic schizophrenics using a computerized assessment of the multiple components of attentional function. Two comparable samples, consisting, respectively, of out-patients and in-patients, were tested in order to assess the effect of chronic institutionalization. Twenty-four subjects (half in-patients and half out-patients) fulfillling DSM-IV criteria for schizophrenia were examined with a standard computerized battery for the assessment of attention, namely Testbatterie zur Aufmerksamkeitsprufung (TAP). Both groups were impaired on all measures of attentional processing (in terms of both reaction times and number of errors). There were no significant differences in attentional performance between in- and out-patients. In conclusion, the present findings confirm the presence of pervasive attentional dysfunction in chronic schizophrenia; the lack of significant differences in performance between in- and out-patients supports the hypothesis that the cognitive deficits are inherently associated with the illness and cannot be attributed to environmental/social factors. [source] Correlation of panic attacks and hostility in chronic schizophreniaPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2001Ching-Yen Chen MD Abstract The aim of this study was to investigate the relationship between panic attacks and hostility in patients with chronic schizophrenia. Thirty-two patients with a minimum 2-year history of treatment for schizophrenia were interviewed. The patients took mood stablizers lithium, carbamazepine and valproate adjunctively for hostility and anger attacks. Panic attacks were defined by Structure Clinical Interview of DSM-IV. Severity of psychopathology was assessed by the Hamilton Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale (BPRS). Functional level was assessed by the Global Assessment of Functioning Scale (GAF). Eight (25%) patients met the diagnostic criteria for panic attacks (DSM-IV) with affective symptoms including hostility and sudden spells of anger. Their HDRS scores were significantly higher (P < 0.01), and GAF scores were significantly lower (P < 0.05) than those of patients without panic attacks. Patients with panic attacks displayed significantly higher hostility in the score of the BPRS (P = 0.01). Those who received higher doses of neuroleptics were more likely to be considered hostile. Multivariate analysis revealed that panic attacks were correlated with more severe depression, greater hostility and lower GAF scores. The results suggest that increased hostility and anger spells may be symptoms of panic attacks, which are overlooked by psychiatrists. [source] Personal stigma and coping strategies in families of patients with schizophrenia: Comparison between Japan and KoreaASIA-PACIFIC PSYCHIATRY, Issue 2 2010Setsuko Hanzawa PhD Abstract Introduction: It has been extensively documented that caregivers of persons who have serious and persistent mental disorders must successfully cope with many challenging problems in order to provide good care. However, little is known about the relationship between family stigma and strategies for coping with patients with schizophrenia. Therefore, the present study compared the personal stigma and coping strategies of families of patients with schizophrenia by examining the socio-cultural factors that affect the care experience of families in Northeast Asian countries. Methods: Two self-rating scales were used to compare personal stigma and coping strategies regarding family members of patients with schizophrenia in 47 Japanese and 92 Korean families. Respondents reported their personal attitudes (personal stigma) with respect to a case vignette that described a person with chronic schizophrenia. Results: Analysis revealed the following: 1) although no differences in coping strategies were observed between the countries, the personal stigma of families was significantly higher in Korea than in Japan; 2) coping strategies, such as positive communication, coercion, and avoidance, were significantly associated with personal stigma in Korean families; however, in Japanese families, resignation was significantly associated with personal stigma. Discussion: The present findings suggest that personal family stigma was higher in Korea than Japan, and the features associated with coping strategies differ between countries. It is important to determine the features of personal stigma that are associated with schizophrenia. Furthermore, education and support programs for families with schizophrenia based on trans-cultural considerations must be emphasized in both countries. [source] Family stigma and care burden of schizophrenia patients: Comparison between Japan and KoreaASIA-PACIFIC PSYCHIATRY, Issue 3 2009Setsuko Hanzawa PhD Abstract Introduction: In the present study, we compared the care burden and stigma experienced by families of patients with schizophrenia in Japan (Niigata) and Korea (Seoul and Daegu) to elucidate similarities and differences in the sociocultural factors that affect the care experience of families in East Asia. Methods: Factors such as care burden (evaluated using the eight-item short version of the Zarit Caregiver Burden Interview [ZBI-8]), stigma, and social distance were evaluated in members of support groups for families of mentally ill individuals in Japan (n=47) and Korea (n=92) using an interview questionnaire. Interviewees reported their personal attitudes (personal stigma and social distance) and perceptions of the attitudes of others in the community (perceived stigma) with respect to a case vignette. These vignettes described a person with chronic schizophrenia. Results: The data analysis revealed the following: (i) feelings of care burden (according to ZBI-8), perceived stigma, and social distance were significantly stronger in Japan compared to Korea, and (ii) feelings of personal stigma were significantly stronger in Korea than in Japan. Discussion: The care burden and stigma experienced by families of patients with schizophrenia differed between Japan and Korea. The present findings suggest that to provide effective support for reducing family stigma and care burden, the necessity of such support must be emphasized in both countries. [source] Validation of Surrogate Markers in Multiple Randomized Clinical Trials with Repeated MeasurementsBIOMETRICAL JOURNAL, Issue 8 2003Ariel Alonso Abstract Part of the recent literature on the validation of biomarkers as surrogate endpoints proposes to undertake the validation exercise in a multi-trial context which led to a definition of validity in terms of the quality of both trial level and individual level association between the surrogate and the true endpoints (Buyse et al., 2000). These authors concentrated on continuous univariate responses. However, in many randomized clinical studies, repeated measurements are encountered on either or both endpoints. When both the surrogate and true endpoints are measured repeatedly over time, one is confronted with the modelling of bivariate longitudinal data. In this work, we show how such a joint model can be implemented in the context of surrogate marker validation. In addition, another challenge in this setting is the formulation of a simple and meaningful concept of "surrogacy". We propose the use of a new measure, the so-called variance reduction factor, to evaluate surrogacy at the trial and individual level. On the other hand, most of the work published in this area assume that only one potential surrogate is going to be evaluated. We also show that this concept will let us evaluate surrogacy when more than one surrogate variable is available for the analysis. The methodology is illustrated on data from a meta-analysis of five clinical trials comparing antipsychotic agents for the treatment of chronic schizophrenia. [source] Validation of Surrogate Markers in Multiple Randomized Clinical Trials with Repeated Measurements: Canonical Correlation ApproachBIOMETRICS, Issue 4 2004Ariel Alonso Summary Part of the recent literature on the evaluation of biomarkers as surrogate endpoints starts from a multitrial context, which leads to a definition of validity in terms of the quality of both trial-level and individual-level association between the surrogate and true endpoints (Buyse et al., 2000, Biostatistics1, 49,67). These authors concentrated on cross-sectional continuous responses. However, in many randomized clinical studies, repeated measurements are encountered on either or both endpoints. A challenge in this setting is the formulation of a simple and meaningful concept of "surrogacy."Alonso et al. (2003, Biometrical Journal45, 931,945) proposed the variance reduction factor (VRF) to evaluate surrogacy at the individual level. They also showed how and when this concept should be extended to study surrogacy at the trial level. Here, we approach the problem from the natural canonical correlation perspective. We define a class of canonical correlation functions that can be used to study surrogacy at the trial and individual level. We show that the VRF and the R2 measure defined by Buyse et al. (2000) follow as special cases. Simulations are conducted to evaluate the performance of different members of this family. The methodology is illustrated on data from a meta-analysis of five clinical trials comparing antipsychotic agents for the treatment of chronic schizophrenia. [source] Comments on ,Cost-effectiveness of antipsychotics for outpatients with chronic schizophrenia'INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2008S. S. Koh No abstract is available for this article. [source] | ||||||||||||||||