This issue of CNS Spectrums represents a milestone for both those affected by autism and related disorders and for clinicians and researchers who provide help and support to these individuals. In order to improve the lives of a rapidly increasing number of patients with this diagnosis, it is critical for the medical and research community to apply a collaborative and consistent strategy for clinical studies in autism.

The five articles that follow are a synopsis of the five subcommittees of the Autism Clinical Trials Task Force (ACTTF), a collaborative panel of experts convened by the Cure Autism Now (CAN) foundation in the spring of 2002. These subcommittees focused on key issues in clinical trials of autism, including subject selection, outcome measures, study design, biological measures, and governmental issues. CAN brought together this panel of participants from academia, government, and industry for the ACTTF think tank. The panel was organized and chaired by Eric Hollander, MD, and Ricki Robinson, MD, MPH. The overarching goal was to clarify what was known about the state of the art of the field in this area, what key information was still unknown, and to implement specific approaches and suggestions for studies which would provide information to fill in the missing gaps in our knowledge base.

The goal of psychopharmacohgic research in autism is to provide guidance to clinicians and families on the risks and benefits of specific interventions. Careful subject selection and subject characterization in clinical trials are necessary for replication, to inform clinicians about the sample, and to elucidate the type of patients who might benefit from, the treatment. At minimum, subject characterization includes demographic information, diagnosis (autism, Åsperger's syndrome, or pervasive developmental disorder-not otherwise specified), intellectual functioning, adaptive functioning, symptom severity, general behavioral profile, health status, pertinent clinical laboratory measures, height, weight, current treatments, and educational placements. Subject selection, sample size, and choice of the primary outcome measure are closely interrelated and linked to the study hypothesis. The magnitude of expected improvement on the primary outcome measure, which can be expressed by effect size, has direct implications for sample size. Large sample sizes are required to detect small effect sizes. To facilitate interpretation of study results, research reports should provide descriptive characteristics of the sample as well as the mean change and standard deviation on the primary outcome measure data to permit calculation of the effect size.

This paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs). The Clinical Global Impressions scale was recommended for all randomized clinical trials. At this point, however, there is no “perfect” choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across the age range. In trials where the intention is to alter core features of ASDs, adaptive behavior scales are also worthy of consideration. Several “behavior complexes” common to ASDs are identified, and instruments are recommended for assessment of these. Given the prevalence of cognitive impairment in ASDs, it is important to assess any cognitive effects, although cognitive data from ASD randomized clinical trials, thus far, are minimal. Guidance from trials in related pharmacologic areas and behavioral pharmacology may be helpful. We recommend routine elicitation of side effects, height and weight, vital signs, and (in the case of antipsychotics) extrapyramidal side-effects assessment. It is often appropriate to include laboratory tests and assessments for continence and sleep pattern.

There are specific challenges to studying the design of pharmacologic trials in child/adolescent and adult autism, such as subject stratification and parallel versus crossover designs. This article describes how optimal study design is influenced by subject selection and outcome measures chosen. Lessons learned in study design from the Research Units on Pediatric Psychopharmacology Autism Network trial with risperidone, Seaver Center trials with fluoxetine and valproate, Dartmouth trials with amantadine, and National Institutes of Health secretin trials are highlighted. The Internet System for Assessing Autistic Children system for managing multicenter clinical trials in autism and statistical issues in autism research are also described.

Biomedical measures are critical in the initial patient-screening and -selection phases of a clinical trial in autism and related disorders. These measures can also play an important role in the assessment and characterization of response and can provide an opportunity to study underlying etiologic and pathophysiologic processes. Thus, biomedical measures, including clinical laboratory analyses, metabolic screening, and chromosomal analysis, are used to screen for potential safety-related problems, to decrease biological and genetic heterogeneity, and to define subgroups. Neurobiological measures can be examined as possible predictors, modifiers or surrogates of therapeutic response, and adverse effects. Neurobiological research measures can also be used to study mechanisms and extent of drug action and to perform baseline and longitudinal investigations of possible pathophysiologic alterations. The potential utility and desirability of specific measures are considered and the general approach to choosing measures for incorporation is discussed.

Randomized clinical trials remain the most valid method of testing the efficacy and safety of treatments. While efforts to elucidate the genetic and neurodevelopmental bases of autism are underway, clinicians and families are in need of scientifically valid information on how to best treat patients with autism. The effectiveness of many interventions currently used in communities has not been adequately tested. Given the high public health relevance of autism treatment research and the low interest of the pharmaceutical industry in autism, the role of the National Institutes of Health in supporting this research is paramount. Among recently launched initiatives in autism clinical trials, there are the Research Units on Pediatric Psychopharmacology Autism Network and the network of centers for Studies to Advance Autism Research and Treatment. These and other government activities in the area of autism clinical trials are here briefly reviewed.

A 56-year-old male presented with compulsive hoarding along with attention-deficit/hyperactivity disorder and schizotypal personality disorder. Hoarding has been described as difficult to treat both pharmacologically and behaviorally, and this patient's comorbid conditions also contributed to his overall impairment. The patient's treatment regimen of fluvoxamine, amphetamine salts, and risperidone, along with behavioral therapy, has helped with hoarding behaviors, motivation, procrastination, and increased socialization. Hoarding may be a unique subtype of obsessive-compulsive disorder with poorer prognosis and distinct neuroanatomic dysfunction. Augmentation with stimulants may provide benefits in aspects of hoarding such as procrastination, especially in patients with comorbid attention-deficit hyperactivity disorder.