Innovations In Clinical Neuroscience

NOV-DEC 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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31 ICNS INNOVATIONS IN CLINICAL NEUROSCIENCE November-December 2017 • Volume 14 • Number 11–12 O R I G I N A L R E S E A R C H functional outcome than expressive deficits. 6,9–11 This finding has also been observed in clinical high risk populations. 12 Additionally, the magnitude of impairment in experiential deficits, but not in expressive deficits, has been shown to be associated with employment outcomes of fewer hours worked and lesser wages earned. 13 Recent work has suggested that experiential deficits and expressive deficits might identify different clusters of patients, meaning that there might be distinct subgroups of patients with primary impairments in emotional experience and expression. 14 These findings suggest that an individual assessment of both negative symptom dimensions might increase the sensitivity of treatment outcome. 15 Given the marked heterogeneity in schizophrenia symptoms, the ability to more precisely differentiate the pathological mechanisms of the two negative-symptom dimensions across symptom severity levels and geographical regions is critically important for the development of effective treatment interventions. Many psychometric measurements, especially in psychiatry, have items that might perform differently with diverse groups. 16 The Postitive and Negative Syndrome Scale (PANSS), which estimates the latent trait of the intensity of symptoms in schizophrenia, was developed and validated 30 years ago on a hospitalized sample of subjects with chronic schizophrenia, without accounting for group differences across highly important domains. 17 Therefore, evidence for the validity of inferences made from symptom scores includes an evaluation of group differences (e.g., geographical regions) in symptom presentation. The presence of bias in ratings and the impact of symptoms on overall functioning is of interest. Scores that perform in markedly different ways across demographic, regional, cultural, or clinical severity characteristics might not be valid representations of the target construct. Our previous studies have shown that the PANSS might not be equivalently rated across country- specific and cultural disparities, not only with regard to symptom expression but also with respect to rater judgment of symptom severity scores. 18 When looking at comparisons of reliability estimates across geo-cultural groups, Khan et al 18 found increased variability among those scores of the PANSS Negative Symptoms subscale that had the lowest reliability. The investigators further observed differential item functioning (DIF) for the PANSS Negative Symptoms subscale as compared with the PANSS Positive Symptoms and General Psychopathology subscales. The DIF method estimates the difference in the probability of raters from different countries scoring symptoms similarly when assessing subjects of the same severity level. Theoretically, if an item is free of construct-irrelevant variance, then subjects with the same severity level—even if scored by different raters, and regardless of geographical location—should have the same probability of a similar symptom presentation on that item. When a statistically significant difference in probability is observed, the following might have contributed to the difference: ambiguity of the description of the item/symptom being measured; issues with rater training, rater difficulty in comprehending the construct being measured, subject's severity level; language or translation validity; and influence due to geographical characteristics. Despite the extensive psychometric work done on the PANSS for the past 30 years, only within the past 10 years have more modern psychometric techniques (such as item response analysis and DIF) been applied to the PANSS. In general, the use of these techniques is done during scale development as opposed to post hoc. However, as negative symptoms remain difficult for raters to assess reliably in international clinical trials 19 and across cultures, 18,20 using these techniques post hoc can help to further elucidate the psychometric properties of negative symptom assessments by identifying their validity and reliability across international trials. Existing research has already shown that a two-factor model of the PANSS fits negative symptoms data significantly better than a one-factor model. 15 The purpose of this article is to 1) assess the replicability of the two-factor solution of negative symptoms (expressive deficits and experiential deficits) commonly found in people with schizophrenia or schizoaffective disorder, and people at clinical high risk of psychosis 1,5,12,15,21 and 2) compare items with differential functioning across geographical regions. The results of this study can be used to customize and guide protocol development and rater training. METHODS Sample. Data were provided for 7,348 subjects who were enrolled between 1992 and 2005 in one of 16 randomized, double- blind clinical trials comparing risperidone, risperidone depot, or paliperidone to other antipsychotic drugs (e.g., haloperidol, olanzapine) or a placebo (information on these trials is presented in Appendix 1). As these were comparative open-label and double- blind trials examining the safety and efficacy of antipsychotics, subjects included in these studies were selected based on overall symptom presentation, rather than primarily on the severity of negative symptoms. The data used in the current analysis comprise the baseline (pre-treatment) data collected in these trials, but can be seen as representative of individuals who enter multicenter, international clinical trials. All studies were carried out in accordance with the latest version of the Declaration of Helsinki. Study procedures were reviewed by the respective ethics committees, and informed consent was obtained from all subjects after the procedures were fully explained. Data analysis included baseline PANSS item scores from 6,889 out of the 7,348 subjects for whom data was provided. A total of 459 subjects (6.25%) were removed from the analysis. Of these 459 subjects, 92 (20.04%) were removed due to having diagnoses other than schizophrenia or schizoaffective disorder. An additional three subjects (0.65%) with no reported diagnosis and two subjects (0.44%) with missing PANSS item scores were removed. Lastly, 362 subjects were removed from geographical regions that did not have an adequate sample size (at least 100 subjects per group as required for the DIF analysis). Data source. Data for the analysis were provided by Ortho-McNeil Janssen Pharmaceuticals, Inc. (Raritan, New Jersey, USA). The data for each subject included a study identifier, de-identified subject number, sex, age at the time of study entry, age at the time of onset of illness, medication to which subject was randomized, country of residence during the time of study participation, and scores for each of the 30 PANSS items at the baseline visit. To maintain confidentiality, no treatment code information was included in the data, nor did any exchange of information occur that could have identified either the subjects or the investigative sites participating in the studies.

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