Assessment in multisite randomized clinical trials of patients with autistic disorder: The autism RUPP network

Assessment of autistic disorder (autism) symptoms, primary and secondary, p oses more challenging problems than ordinarily found in multisite randomize d clinical trial (RCT) assessments. For example, subjects may be uncommunic ative and extremely heterogeneous in problem presentation, and current phar macological treatments are not likely to alter most core features of autism . The Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Ne twork) resolved some of these problems during the design of a risperidone R CT in children/adolescents. The inappropriateness of the usual anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining u ncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The communication problems, compromising use of the patient as an informan t, were addressed by several strategies, including careful questioning of c are providers, rating scales, laboratory tests, and physical exams. The bro ad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects. The pro blems of neuropsychologically testing nonverbal, lower functioning, sometim es noncompliant subjects requires careful instrument selection/adaptation a nd flexible administration techniques. The problems of assessing low-end IQ s, neglected by most standardized test developers, was resolved by an algor ithm of test hierarchy. Scarcity of other autism-adapted cognitive and neur opsychological tests and lack of standardization required development of a new, specially adapted battery. Reliability on the Autism Diagnostic Interv iew (currently the most valid diagnostic instrument) and other clinician in struments required extensive cross-site training (in-person, videotape, and teleconference sessions). Definition of a treatment responder required foc us on individually relevant target symptoms, synthesis of possible modest i mprovements in many domains, and acceptance of attainable though imperfect goals. The assessment strategy developed is implemented in a RCT of risperi done (McDougle et al., 2000) for which the design and other methodological challenges are described elsewhere (Scahill et al., 2000). Some of these pr oblems and solutions are partially shared with RCTs of other treatments and other disorders.