Recommendations for the Electronic Migration and Implementation of Clinician-Reported Outcome Assessments in Clinical Trials.

OBJECTIVES: Although best practices from electronic patient-reported outcome (PRO) measures are transferable, the migration of clinician-reported outcome (ClinRO) assessments to electronic modes requires recommendations that address their unique properties, such as the user (eg, clinician), and complexity associated with programming of clinical content. Faithful migration remains essential to ensuring that the content and psychometric properties of the original scale (ie, validated reference) are preserved, such that clinicians completing the ClinRO assessments interpret and respond to the items the same way regardless of data collection mode. The authors present a framework for how to "faithfully" migrate electronic ClinRO assessments for successful deployment in clinical trials. METHODS: Critical Path Institute's Electronic PRO Consortium and PRO Consortium convened a consensus panel of representatives from member firms to develop recommendations for electronic migration and implementation of ClinRO assessments in clinical trials based on industry standards, regulatory guidelines where available, and relevant literature. The recommendations were reviewed and approved by all member firms from both consortia. CONSENSUS RECOMMENDATIONS: Standard, minimal electronic modifications for ClinRO assessments are described. This article also outlines implementation steps, including planning, startup, electronic clinical outcome assessment system development, training, and deployment. The consensus panel proposes that functional clinical testing by a clinician or clinical outcome assessment expert, as well as copyright holder review of screenshots (if possible) are sufficient to support minimal modifications during migration. Additional evidence generation is proposed for modifications that deviate significantly from the validated reference.

Spatial working memory deficits in autism.

Previous studies have reported working memory deficits in autism, but this finding has been inconsistent. One possibility is that deficits in this domain may be present only when working memory load exceeds some limited capacity. High-functioning individuals with autism performed the CANTAB computerized test of spatial working memory. Individuals with autism made more errors than a matched group of typically developing controls on this task, and were less likely to consistently use a specific organized search strategy to complete the task. Overall, these results demonstrate reduced spatial working memory abilities in autism, and extend previous findings by demonstrating that these deficits are significant when tasks impose heavier demands on working memory.

Brief report: developmental change in theory of mind abilities in children with autism.

This longitudinal study investigated developmental change in theory of mind among 57 children with autism aged between 4 to 14 years at the start of the study. On an initial visit and one year later, each participant was administered a battery of tests designed to measure a broad developmental range of theory of mind abilities from early (e.g., desire) to more advanced (e.g., moral judgment) mental state understanding. Both group and individual data indicated significant developmental improvement in theory of mind ability, which was primarily related to the children's language abilities.

The Repeatable Battery for the Assessment of Neuropsychological Status effort scale.

The measurement of effort is now considered to be an important component of neuropsychological assessment. In addition to stand-alone measures, built-in, or embedded measures of effort have been derived for a limited number of standard neurocognitive tests. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a widely used brief battery, employed as a core diagnostic tool in dementia and as a neurocognitive screening battery or tracking/outcome measure in a variety of other disorders. An effort index (EI) for the RBANS has been published previously (Silverberg, N. D., Wertheimer, J. C., & Fichtenberg, N. L. 2007. An EI for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Clinical Neuropsychology, 21 (5), 841-854), but it has been reported to result in high false positive rates when applied to patients with "true" amnesia (e.g., Alzheimer's disease). We created a new effort scale (ES) for the RBANS based on the observation of patterns of free recall and recognition performance in amnesia versus inadequate effort. The RBANS ES was validated on a sample of patients with amnestic disorders and a sample of mild traumatic brain injury participants who failed a separate measure of effort. The sensitivity and specificity of the new ES was compared with the previously published EI. Receiver-operating characteristic analyses demonstrated much better sensitivity and specificity of the ES, with a marked reduction in false positive errors. Application and limitations of the RBANS ES, including indications for its use, are discussed.

Cerebellum, language, and cognition in autism and specific language impairment.

We performed cerebellum segmentation and parcellation on magnetic resonance images from right-handed boys, aged 6-13 years, including 22 boys with autism [16 with language impairment (ALI)], 9 boys with Specific Language Impairment (SLI), and 11 normal controls. Language-impaired groups had reversed asymmetry relative to unimpaired groups in posterior-lateral cerebellar lobule VIIIA (right side larger in unimpaired groups, left side larger in ALI and SLI), contralateral to previous findings in inferior frontal cortex language areas. Lobule VIIA Crus I was smaller in SLI than in ALI. Vermis volume, particularly anterior I-V, was decreased in language-impaired groups. Language performance test scores correlated with lobule VIIIA asymmetry and with anterior vermis volume. These findings suggest ALI and SLI subjects show abnormalities in neurodevelopment of fronto-corticocerebellar circuits that manage motor control and the processing of language, cognition, working memory, and attention.

Lateralized response timing deficits in autism.

BACKGROUND: Procedural learning is an implicit process in which a behavioral response is refined through repeated performance. Neural systems supporting this cognitive process include specific frontostriatal systems responsible for the preparation and timing of planned motor responses. Evaluating performance on procedural learning tasks can provide unique information about neurodevelopmental disorders in which frontostriatal disturbances have been reported, such as autism. METHODS: Fifty-two individuals with autism and 54 age-, IQ-, and gender-matched healthy individuals performed an oculomotor serial reaction time task and a sensorimotor control task. RESULTS: Whereas the rate of procedural learning and the precision of planned motor responses were unimpaired in autism, a lateralized alteration in the ability to time predictive responses was observed. Rightward saccadic responses were speeded in individuals with autism relative to healthy control subjects. CONCLUSIONS: Speeded rightward predictive saccades suggest atypical functioning of left hemisphere striatal chronometric systems in autism.

Activation of the fusiform gyrus when individuals with autism spectrum disorder view faces.

Prior imaging studies have failed to show activation of the fusiform gyrus in response to emotionally neutral faces in individuals with autism spectrum disorder (ASD) [Critchley et al., Brain 124 (2001) 2059; Schultz et al., Arch. Gen. Psychiatry 57 (2000) 331]. However, individuals with ASD do not typically exhibit the striking behavioral deficits that might be expected to result from fusiform gyrus damage, such as those seen in prosopagnosia, and their deficits appear to extend well beyond face identification to include a wide range of impairments in social perceptual processing. In this study, our goal was to further assess the question of whether individuals with ASD have abnormal fusiform gyrus activation to faces. We used high-field (3 T) functional magnetic resonance imaging to study face perception in 11 adult individuals with autism spectrum disorder (ASD) and 10 normal controls. We used face stimuli, object stimuli, and sensory control stimuli (Fourier scrambled versions of the face and object stimuli) containing a fixation point in the center to ensure that participants were looking at and attending to the images as they were presented. We found that individuals with ASD activated the fusiform face area and other brain areas normally involved in face processing when they viewed faces as compared to non-face stimuli. These data indicate that the face-processing deficits encountered in ASD are not due to a simple dysfunction of the fusiform area, but to more complex anomalies in the distributed network of brain areas involved in social perception and cognition.