Hostname: page-component-8448b6f56d-xtgtn Total loading time: 0 Render date: 2024-04-24T13:47:30.446Z Has data issue: false hasContentIssue false
  • English
  • Français

Subject Selection and Characterization in Clinical Trials in Children with Autism

Published online by Cambridge University Press:  07 November 2014

Lawrence Scahill  and
Catherine Lord
Get access Rights & Permissions [Opens in a new window]

Abstract

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.

Type
Review Article
Information
CNS Spectrums , Volume 9 , Issue 1 , January 2004 , pp. 22 - 32
Copyright
Copyright © Cambridge University Press 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.McDougle, CJ, Posey, DJ. Autistic and other pervasive developmental disorders. In Martin, A, Scahill, L, Charney, DS, Leckman, JF, eds. Pediatric Psychopharmacology: Principles and Practice. New York, NY: Oxford University Press; 2003:563–579.Google Scholar
2.Aman, MG, Novotny, S, Samango-Sprouse, C, et al.Outcome measures for clinical trials in autism. CNS Spectr. 2003;9:36–47.CrossRefGoogle Scholar
3.Martin, A, Koenig, K, Anderson, GM, Scahill, L. Low-dose fluvoxamine treatment of children and adolescents with pervasive developmental disorders: a prospective, open-label study. J Autism Dev Disord. 2003;33:77–85.CrossRefGoogle ScholarPubMed
4.RUPP Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002;347:314–321.CrossRefGoogle Scholar
5.Begg, C, Cho, M, Eastwood, S, et al.Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA. 1996;276:637–639.CrossRefGoogle ScholarPubMed
6.Arnold, LE, Aman, MG, Martin, A, et al.Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric Psychopharmacology. J Autism Dev Disord. 2000;30:99–111.CrossRefGoogle ScholarPubMed
7.Lord, C, McGee, JP. Educating Children with Autism. Washington, DC: National Academy Press; 2001.Google Scholar
8.Lord, C, Pickles, A, McLemman, J, et al.Diagnosing autism: analyses of data from the Autism Diagnostic Interview. J Autism Dev Disord. 1997;27:501–517.CrossRefGoogle ScholarPubMed
9.Lord, C, Risi, S, Lambrecht, L, et al.The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000;30:205–223.CrossRefGoogle ScholarPubMed
10.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington DC: American Psychiatric Association; 1994.Google Scholar
11.World Health Organization. The ICD-10 Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva, Switzerland; 1992.Google Scholar
12.Lord, C, Storoschuk, S, Rutter, M, et al.Using the ADI-R to diagnose autism in preschool children. Infant Ment Health J. 1993;14:234–252.3.0.CO;2-F>CrossRefGoogle Scholar
13.Nordin, V, Gillberg, C. Autism spectrum disorders in children with physical or mental disability or both. II: Screening aspects. Dev Med Child Neurol. 1996;38:314–324.CrossRefGoogle ScholarPubMed
14.Schopler, E, Reichler, RJ, Renner, BR. The Childhood Autism Rating Scale (CARS) for Diagnostic Screening and Classification in Autism. Los Angeles, Calif: Western Psychological Services; 1988.Google Scholar
15.Cox, A, Klein, K, Charman, T, et al.Autism spectrum disorders at 20 and 42 months of age: stability of clinical and ADI-R diagnosis. J Child Psychol Psychiatry. 1999;40:719–732.CrossRefGoogle ScholarPubMed
16.Lord, C. Follow-up of two-year-olds referred for possible autism J Child Psychol Psychiatry. 1995;36:1365–1382.CrossRefGoogle ScholarPubMed
17.Constantino, JN. The Social Responsiveness Scale. Los Angeles, Calif: Western Psychological Services; 2002.Google Scholar
18.South, M, Williams, BJ, McMahon, WM, et al.Utility of the Gilliam Autism Rating Scale in research and clinical populations. J Autism Dev Disord. 2002;32:593–599.CrossRefGoogle ScholarPubMed
19.Volkmar, FR, Cicchetti, DV, Dykens, E, Sparrow, SS, Leckman, JF, Cohen, DJ. An evaluation of the Autism Behavior Checklist. J Autism Dev Disord. 1988;18:81–97.CrossRefGoogle ScholarPubMed
20.Yirmiya, N, Sigman, M, Freeman, BJ. Comparison between diagnostic instruments for identifying high-functioning children with autism. J Autism Dev Disord. 1994;24:281–291.CrossRefGoogle ScholarPubMed
21.Wechsler, D. Wechsler Abbreviated Scale of Intelligence. San Antonio, Tex: Psychological Corporation; 1999.Google Scholar
22.Wechsler, D. Wechsler Intelligence Scale for Children. 3rd ed. San Antonio, Tex: Psychological Corporation; 1992.Google Scholar
23.Raven, JC. Raven's Progressive Matrices and Vocabulary Scales. London, England: H. K. Lewis; 1986.Google Scholar
24.Elliott, CD. Differential Abilities Scale (DAS). San Antonio, Tex: Psychological Corporation; 1990.Google Scholar
25.Mullen, E. Mullen Scales of Early Learning. Los Angeles, Calif: Western Psychological Services; 1997.Google Scholar
26.Sparrow, S, Balla, D, Cicchetti, D. Vineland Scales of Adaptive Behavior, Survey Form Manual. Circle Pines, Minn: American Guidance Service; 1984.Google Scholar
27.Dunn, LM. Peabody Picture Vocabulary Test. 3rd ed. Circle Pines, Minn: American Guidance Service; 1997.Google Scholar
28.Venter, A, Lord, C, Schopler, E. A follow-up study of high-functioning autistic children. J Child Psychol Psychiatry. 1992;33:489–507.CrossRefGoogle ScholarPubMed
29.Tager-Flusberg, H, Sullivan, K. Predicting and explaining behavior: a comparison of autistic, mentally retarded and normal children. J Child Psychol Psychiatry. 1994;35:1059–1075.CrossRefGoogle ScholarPubMed
30.Szatmari, P, Merette, C, Bryson, SE, et al.Quantifying dimensions in autism: a factor-analytic study. J Am Acad Child Adolesc Psychiatry. 2002;41:467–474.CrossRefGoogle ScholarPubMed
31.Pocock, SJ. Clinical Trials: A Practical Approach. Chichester, England: John Wiley & Sons; 1993.Google Scholar
32.Kraemer, HC. To increase power in randomized clinical trials without sample size. Psychopharmacol Bull. 1991;27:217–224.Google ScholarPubMed
33.Kern, JK, Van Miller, S, Evans, PA, Trivedi, MH. Efficacy of porcine secretin in children with autism and pervasive developmental disorder. J Autism Dev Disord. 2002;32:153–160.CrossRefGoogle ScholarPubMed
34.Cohen, J. Statistical Power Analysis for the Behavioral Sciences. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988.Google Scholar
35.Borenstein, M, Rothstein, H, Cohen, J. Power and Precision. Englewood, NJ: Biostat, Inc.; 2001.Google Scholar
36.Meinert, CL. Clinical Trials: Design, Conduct, and Analysis. New York, NY: Oxford University Press; 1986.CrossRefGoogle Scholar
37.Vitiello, B. Clinical trials methodology and design issues. In: Martin, A, Scahill, L, Charney, DS, Leckman, JF, eds. Pediatric Psychopharmacobgy: Principles and Practice. New York, NY: Oxford University Press; 2003:712–724.Google Scholar
38.King, BH, Wright, DM, Handen, BL, et al.Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. J Am Acad Child Adolesc Psychiatry. 2001;40:658–665.CrossRefGoogle ScholarPubMed
39.Marshburn, EC, Aman, MG. Factor validity and norms for the aberrant behavior checklist in a community sample of children with mental retardation. J Autism Dev Disord. 1992;22:357–373.CrossRefGoogle Scholar
40.Brown, EC, Aman, MG, Havercamp, SM. Factor analysis and norms for parent ratings on the Aberrant Behavior Checklist-Community for young people in special education. Res Dev Disabil. 2002;23:45–60.CrossRefGoogle ScholarPubMed
41.McDougle, CJ, Posey, D. Genetics of childhood disorders: XLIV. Autism, part 3: psychopharmacology of autism. J Am Acad Child Adolesc Psychiatry. 2002;41:1380–1383.CrossRefGoogle ScholarPubMed
42.Koegel, LK, Koegel, RL, Shoshan, Y, et al.Pivotal response intervention II: preliminary long-term outcome data. J Assoc Pers Sev Handicaps. 1999;24:186–198.Google Scholar
43.Freeman, BJ, Ritvo, ER, Yokota, A, Ritvo, A. A scale for rating symptoms of patients with the syndrome of autism in real life settings. J Am Acad Child Psychiatry. 1986;25:130–136.CrossRefGoogle ScholarPubMed
44.Owley, T, McMahon, W, Cook, EH, et al.Multisite, double-blind, placebo-controlled trial of porcine secretin in autism. J Am Acad Child Adoksc Psychiatry. 2001;40:1293–1299.CrossRefGoogle ScholarPubMed
45.Unis, AS, Munson, JA, Rogers, SJ, et al.A randomized, double-blind, placebo-controlled trial of porcine versus synthetic secretin for reducing symptoms of autism. J Am Acad Child Adolesc Psychiatry. 2002;41:1315–1321.CrossRefGoogle ScholarPubMed
46.Guy, W. ECDEU Assessment Manual for Psychopharmacology. Rev. Rockvillle, Md: U.S. Department of Health, Education, and Human Welfare; publication no. ADM-76-338; 1976.Google Scholar
47.Sandler, AD, Sutton, KA, DeWeese, J, Girardi, MA, Sheppard, V, Bodfish, JW. Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder. N Engl J Med. 1999;341:1801–1806.CrossRefGoogle ScholarPubMed