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Abstract

Assessment of autistic disorder (autism) symptoms, primary and secondary, poses more challenging problems than ordinarily found in multisite randomized clinical trial (RCT) assessments. For example, subjects may be uncommunicative and extremely heterogeneous in problem presentation, and current pharmacological treatments are not likely to alter most core features of autism. The Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Network) resolved some of these problems during the design of a risperidone RCT in children/adolescents. The inappropriateness of the usual anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining uncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The communication problems, compromising use of the patient as an informant, were addressed by several strategies, including careful questioning of care providers, rating scales, laboratory tests, and physical exams. The broad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects. The problems of neuropsychologically testing nonverbal, lower functioning, sometimes noncompliant subjects requires careful instrument selection/adaptation and flexible administration techniques. The problems of assessing low-end IQs, neglected by most standardized test developers, was resolved by an algorithm of test hierarchy. Scarcity of other autism-adapted cognitive and neuropsychological tests and lack of standardization required development of a new, specially adapted battery. Reliability on the Autism Diagnostic Interview (currently the most valid diagnostic instrument) and other clinician instruments required extensive cross-site training (in-person, videotape, and teleconference sessions). Definition of a treatment responder required focus on individually relevant target symptoms, synthesis of possible modest improvements in many domains, and acceptance of attainable though imperfect goals. The assessment strategy developed is implemented in a RCT of risperidone (McDougle et al., 2000) for which the design and other methodological challenges are described elsewhere (Scahill et al., 2000). Some of these problems and solutions are partially shared with RCTs of other treatments and other disorders.

A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder

“…Additional inclusion criteria included a clinician Clinical Global Impression scale of Severity (of autistic symptoms) of C3 (Arnold et al 2000) and a history of chronic, persistent GI disturbance based on Rome II Criteria for the diagnosis of irritable bowel syndrome. These criteria included GI disturbance of C6 weeks duration, which did not need to be consecutive, during the last 3 months of either (1) constipation predominant (defined as B2 bowel movements (BM) per week described as lumpy or hard), (2) diarrhea predominant (defined as C3 loose BM/day or C1 watery BM/day), or (3) alternating periods of constipation and diarrhea as defined above.…”

Risperidone Treatment of Autistic Disorder: Longer-Term Benefits and Blinded Discontinuation After 6 Months

“…The screening measures also included intelligence testing, the Vineland Adaptive Behavior Scales (12,13), routine laboratory tests, an electrocardiogram, measurements of height, weight, and vital signs, a medical history, and a physical examination. All subjects were also required to manifest clinically significant problems consisting of aggression, tantrums, and/or self-injury as defined by a score of 18 or higher on the irritability subscale of the Aberrant Behavior Checklist-Community version (14,15) rated by the parent (or primary caretaker) and confirmed by clinician review.…”

Augmented feedback in autistic disorder

“…These children avoid eye contact and seem to look past others (Daou et al 2014). These deficits in eye contact may contribute to difficulties in language acquisition and social responsiveness because of diminished object and person engagement and social interaction regulation (Arnold et al 2000;Carbone et al 2013;Kékes Szabó & Szokolszky 2013;Senju et al 2008). Various factors, including sensory modulation, contribute to atypical eye contact in children with AD (Arnold et al 2000;Carbone et al 2013;Bhat, Landa & Galloway 2011;Senju et al 2008).…”

“…These deficits in eye contact may contribute to difficulties in language acquisition and social responsiveness because of diminished object and person engagement and social interaction regulation (Arnold et al 2000;Carbone et al 2013;Kékes Szabó & Szokolszky 2013;Senju et al 2008). Various factors, including sensory modulation, contribute to atypical eye contact in children with AD (Arnold et al 2000;Carbone et al 2013;Bhat, Landa & Galloway 2011;Senju et al 2008). Evidence for and details regarding these possible factors are scarce (Arnold et al 2000;Bhat et al 2011;Carbone et al 2013;Senju et al 2008), but there are indications that children with AD present with atypical processing of eye contact in the occipital lobe, in most instances (Senju et al 2008).…”

“…Various factors, including sensory modulation, contribute to atypical eye contact in children with AD (Arnold et al 2000;Carbone et al 2013;Bhat, Landa & Galloway 2011;Senju et al 2008). Evidence for and details regarding these possible factors are scarce (Arnold et al 2000;Bhat et al 2011;Carbone et al 2013;Senju et al 2008), but there are indications that children with AD present with atypical processing of eye contact in the occipital lobe, in most instances (Senju et al 2008). The gaze-avoidance theory states that children with AD become negatively over-aroused by direct gaze during sensory modulation and consequently avoid it (Kylliäinen et al 2012).…”