Impact of the Early Start Denver Model on the cognitive level of children with autism spectrum disorder: study protocol for a randomised controlled trial using a two-stage Zelen design

Sandrine Touzet, Pauline Occelli, Carmen Schröder, Sabine Manificat, Ludovic Gicquel, Razvana Stanciu, Marie Schaer, Marie-Joelle Oreve, Mario Speranza, Angelique Denis, Amelie Zelmar, Bruno Falissard, Nicolas Georgieff, Stephane Bahrami, Marie-Maude Geoffray, IDEA Study Group, Stéphane Grisi, Stéphanie Marignier, Jean-Marc Useo, Alain Pourrat, Chloé Peter, Flavia Mengarelli, Natacha Gallifet, Fanny Rumillat, Gaelle Tenant, Sandrine Sonié, Marc Zimmerman, Valérie Malo, Céline Grosmaître Jacob, Stéphane Bahrami, Camille Queste, Florence Raffeneau, Sophie Gilet, Mélanie Ammeloot, Anne Danion-Grilliat, Emilie Florence, Valérie Vecchionacci, Lucie Janssen, Anna Dubrovskaya, Monique Rohmer, Bénédicte Lambs, Véronique Delvenne, Sophie Carlier, Lesley Ducenne, Cyrille Colin, Laeticia Bouveret, Sandrine Touzet, Pauline Occelli, Carmen Schröder, Sabine Manificat, Ludovic Gicquel, Razvana Stanciu, Marie Schaer, Marie-Joelle Oreve, Mario Speranza, Angelique Denis, Amelie Zelmar, Bruno Falissard, Nicolas Georgieff, Stephane Bahrami, Marie-Maude Geoffray, IDEA Study Group, Stéphane Grisi, Stéphanie Marignier, Jean-Marc Useo, Alain Pourrat, Chloé Peter, Flavia Mengarelli, Natacha Gallifet, Fanny Rumillat, Gaelle Tenant, Sandrine Sonié, Marc Zimmerman, Valérie Malo, Céline Grosmaître Jacob, Stéphane Bahrami, Camille Queste, Florence Raffeneau, Sophie Gilet, Mélanie Ammeloot, Anne Danion-Grilliat, Emilie Florence, Valérie Vecchionacci, Lucie Janssen, Anna Dubrovskaya, Monique Rohmer, Bénédicte Lambs, Véronique Delvenne, Sophie Carlier, Lesley Ducenne, Cyrille Colin, Laeticia Bouveret

Abstract

Introduction: Early intervention for autism spectrum disorder (ASD) in the European French-speaking countries is heterogeneous and poorly evaluated to date. Early intervention units applying the Early Start Denver Model (ESDM) for toddlers and young children with ASD have been created in France and Belgium to improve this situation. It is essential to evaluate this intervention for the political decision-making process regarding ASD interventions in European French-speaking countries. We will evaluate the effectiveness of 12 hours per week ESDM intervention on the cognitive level of children with ASD, over a 2-year period.

Methods and analysis: The study will be a multicentre, randomised controlled trial, using a two-stage Zelen design. Children aged 15-36 months, diagnosed with ASD and with a developmental quotient (DQ) of 30 or above on the Mullen Scale of Early Learning (MSEL) will be included. We will use a stratified minimisation randomisation at a ratio 1:2 in favour of the control group. The sample size required is 180 children (120 in the control and 60 in the intervention group). The experimental group will receive 12 hours per week ESDM by trained therapists 10 hours per week in the centre and 2 hours in the toddlers' natural environment (alternatively by the therapist and the parent). The control group will receive care available in the community. The primary outcome will be the change in cognitive level measured with the DQ of the MSEL scored at 2 years. Secondary outcomes will include change in autism symptoms, behavioural adaptation, communicative and productive language level, sensory profile and parents' quality of life. The primary analysis will use the intention-to-treat principle. An economic evaluation will be performed.

Dissemination: Findings from the study will be disseminated through peer reviewed publications and meetings.

Trial registration number: NCT02608333 (clinicaltrials.gov); Pre-results.

Keywords: Autism spectrum disorder; Behavior Therapy; Early Start Denver Model; Multicenter Study; Randomized Controlled Trial; Two-stage Zelen design.

Conflict of interest statement

Competing interests: None declared.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
Flow diagram of study protocol. In the two-stage Zelen design, all parents of eligible children consent to participate in a longitudinal observational study, and in a second step, children are randomly allocated to the intervention group.
Figure 2
Figure 2
Schedule of enrolment, interventions and assessments (SPIRIT template).

References

    1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th edn Arlington, VA: American Psychiatric Publishing, 2013.
    1. Charman T, Pickles A, Simonoff E et al. . IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP). Psychol Med 2011;41:619–27. 10.1017/S0033291710000991
    1. Yeargin-Allsopp M. The prevalence and characteristics of autism spectrum disorders in the ALSPAC cohort. Dev Med Child Neurol 2008;50:646 10.1111/j.1469-8749.2008.03059.x
    1. Fombonne E. The prevalence of autism. JAMA 2003;289:87–9. 10.1001/jama.289.1.87
    1. Howlin P. Living with impairment: the effects on children of having an autistic sibling. Child Care Health Dev 1988;14:395–408. 10.1111/j.1365-2214.1988.tb00591.x
    1. Hayes SA, Watson SL. The impact of parenting stress: a meta-analysis of studies comparing the experience of parenting stress in parents of children with and without autism spectrum disorder. J Autism Dev Disord 2013;43:629–42. 10.1007/s10803-012-1604-y
    1. Ganz ML. The lifetime distribution of the incremental societal costs of autism. Arch Pediatr Adolesc Med 2007;161:343–9. 10.1001/archpedi.161.4.343
    1. Salomone E, Beranová Š, Bonnet-Brilhault F et al. . Use of early intervention for young children with autism spectrum disorder across Europe. Autism 2016;20:233–49. 10.1177/1362361315577218
    1. Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci 2013;26:3–31. 10.1177/0952695113484320
    1. Schopler E, Mesibov GB, Hearsey K. Structured teaching in the TEACCH system,1995. In: Schopler E, Mesibov GB eds. Learning and cognition in autism. New York: Kluwer Academic/Plenum, 243––267..
    1. Warren Z, McPheeters ML, Sathe N et al. . A systematic review of early intensive intervention for autism spectrum disorders. Pediatrics 2011;127:e1303–11. 10.1542/peds.2011-0426
    1. Maglione MA, Gans D, Das L et al. . Technical expert panel. Nonmedical interventions for children with ASD: recommended guidelines and further research needs. Pediatrics 2012;130(Suppl 2):S169–78. 10.1542/peds.2012-0900O
    1. Rogers S, Dawson G. Early Start Denver Model for young children with Autism: promoting language, learning, and engagement. Traduit par Rogé. Edition Dunod, Paris: Guilford Press, 2013.
    1. Dawson G, Rogers S, Munson J et al. . Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics 2010;125:e17–23. 10.1542/peds.2009-0958
    1. Fava L, Strauss K. Response to early intensive behavioral intervention for autism--an umbrella approach to issues critical to treatment individualization. Int J Dev Neurosci 2014;39:49–58. 10.1016/j.ijdevneu.2014.05.004
    1. Torgerson DJ, Roland M. What is Zelen's design?. BMJ 1998;316:606 10.1136/bmj.316.7131.606
    1. Campbell R, Peters T, Grant C et al. . Adapting the randomized consent (Zelen) design for trials of behavioural interventions for chronic disease: feasibility study. J Health Serv Res Policy 2005;10:220–5. 10.1258/135581905774414150
    1. Lord C, Rutter M, DiLavore PC et al. . Autism diagnostic observation schedule. Los Angeles, CA: Western Psychological Services, 2012.
    1. Lord C, Rutter M, Le Couteur A. Autism diagnostic interview-revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994;24:659–85. 10.1007/BF02172145
    1. Kim SH, Thurm A, Shumway S et al. . Multisite study of new autism diagnostic interview-revised (ADI-R) algorithms for toddlers and young preschoolers. J Autism Dev Disord 2013;43:1527–38. 10.1007/s10803-012-1696-4
    1. McConachie H, Fletcher-Watson S, Working group 4, COST action ‘enhancing the scientific study of early autism’. Building capacity for rigorous controlled trials in autism: the importance of measuring treatment adherence. Child Care Health Dev 2015;41:169–77. 10.1111/cch.12185
    1. Mullen EM. Mullen scales of early learning. AGS Edition. Circle Pines, MN: American Guidance Service, 1995.
    1. Bishop SL, Guthrie W, Coffing M et al. . Convergent validity of the mullen scales of early learning and the differential ability scales in children with autism spectrum disorders. Am J Intellect Dev Disabil 2011;116:331–43. 10.1352/1944-7558-116.5.331
    1. Swineford LB, Guthrie W, Thurm A. Convergent and divergent validity of the Mullen Scales of early learning in young children with and without autism spectrum disorder. Psychol Assess 2015;27:1364–78. 10.1037/pas0000116
    1. Lord C, Risi S, DiLavore PS et al. . Autism from 2 to 9 years of age. Arch Gen Psychiatry 2006;63:694–701. 10.1001/archpsyc.63.6.694
    1. Pickles A, Anderson DK, Lord C. Heterogeneity and plasticity in the development of language: a 17-year follow-up of children referred early for possible autism. J Child Psychol Psychiatry 2014;55:1354–62. 10.1111/jcpp.12269
    1. Rogers SJ, Estes A, Lord C et al. . Effects of a brief Early Start Denver model (ESDM)-based parent intervention on toddlers at risk for autism spectrum disorders: a randomized controlled trial. J Am Acad Child Adolesc Psychiatry 2012;51:1052–65. 10.1016/j.jaac.2012.08.003
    1. Gotham K, Risi S, Pickles A et al. . The Autism Diagnostic Observation Schedule: revised algorithms for improved diagnostic validity. J Autism Dev Disord 2007;37:613–27. 10.1007/s10803-006-0280-1
    1. Grzadzinski R, Carr T, Colombi C et al. . Measuring changes in social communication behaviors: preliminary development of the Brief Observation of Social Communication Change (BOSCC). J Autism Dev Disord 2016;46:2464–79. 10.1007/s10803-016-2782-9
    1. Sparrow S, Cicchetti DV, Balla DA. Vineland adaptive behavior scales. 2nd edn Vineland™-II: Pearson, 2005.
    1. Wetherby AM, Allen L, Cleary J et al. . Validity and reliability of the communication and symbolic behavior scales developmental profile with very young children. J Speech Lang Hear Res 2002;45:1202–18. 10.1044/1092-4388(2002/097)
    1. Green J, Charman T, McConachie H et al. . Parent-mediated communication-focused treatment in children with autism (PACT): a randomised controlled trial. Lancet 2010;375:2152–60. 10.1016/S0140-6736(10)60587-9
    1. Aldred C, Green J, Emsley R et al. . Brief report: mediation of treatment effect in a communication intervention for pre-school children with autism. J Autism Dev Disord 2012;42:447–54. 10.1007/s10803-011-1248-3
    1. Pickles A, Harris V, Green J et al. . Treatment mechanism in the MRC preschool autism communication trial: implications for study design and parent-focussed therapy for children. J Child Psychol Psychiatry 2015;56:162–70. 10.1111/jcpp.12291
    1. Bassano D, Labrell F, Champaud C, et al. 2005. Le DLPF : Un nouvel outil pour l’évaluation du développement du langage de production en français. Enfance, n°2. Presses universitaires de France. .
    1. Fenson L, Dale PS, Reznick JS et al. . MacArthur communicative development inventory: users guide and technical manual. San Diego, CA: Singular, 1993.
    1. Dunn W. Sensory profile 2 user's manual. San Antonio, TX: Psychological Corporation, 2014.
    1. Hoefman R, Payakachat N, van Exel J et al. . Caring for a child with autism spectrum disorder and parents’ quality of life: application of the CarerQol. J Autism Dev Disord 2014;44:1933–45.
    1. Byford S, Cary M, Barrett B et al. . Cost-effectiveness analysis of a communication-focused therapy for pre-school children with autism: results from a randomised controlled trial. BMC Psychiatry 2015;21:316 10.1186/s12888-015-0700-x
    1. Glick HA, Doshi JA, Sonnad SS et al. . Economic evaluation in clinical trials. 2nd edn Oxford: University Press, 2015.
    1. Schellings R, Kessels AG, ter Riet G et al. . The Zelen design May be the best choice for a heroin-provision experiment. J Clin Epidemiol 1999;52:503–7. 10.1016/S0895-4356(99)00009-8
    1. Homer CSE. Using the Zelen design in randomized controlled trials: debates and controversies. J Adv Nurs 2002;38:200–7. 10.1046/j.1365-2648.2002.02164.x
    1. Adamson J, Cockayne S, Puffer S et al. . Review of randomised trials using the post-randomised consent (Zelen's) design. Contemp Clin Trials 2006;27:305–19. 10.1016/j.cct.2005.11.003
    1. Eapen V, Crnčec R, Walter A. Clinical outcomes of an early intervention program for preschool children with autism spectrum disorder in a community group setting. BMC Pediatr 2013;13:3 10.1186/1471-2431-13-3
    1. Zelen M. Randomized consent designs for clinical trials: an update. Stat Med 1990;9:645–56. 10.1002/sim.4780090611
    1. Brown H, Prescott R. Applied mixed models in medicine. 2nd edn Oxford: Wiley, 2006.
    1. Bearss K, Johnson C, Smith T et al. . Effect of parent training vs parent education on behavioral problems in children with autism spectrum disorder: a randomized clinical trial. JAMA 2015;313:1524–33. 10.1001/jama.2015.3150
    1. Pickles A, Le Couteur A, Leadbitter K et al. . Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial. Lancet 2016;388:2501–9. 10.1016/S0140-6736(16)31229-6
    1. Kasari C, Lawton K, Shih W et al. . Caregiver-mediated intervention for low-resourced preschoolers with autism: an RCT. Pediatrics 2014;134:e72–9. 10.1542/peds.2013-3229
    1. Wetherby AM, Guthrie W, Woods J et al. . Parent-implemented social intervention for toddlers with autism: an RCT. Pediatrics 2014;134:1084–93. 10.1542/peds.2014-0757
    1. Glasgow RE, Lichtenstein E, Marcus AC. Why don't we see more translation of health promotion research to practice? Rethinking the efficacy-to-effectiveness transition. Am J Public Health 2003;93:1261–7. 10.2105/AJPH.93.8.1261
    1. McConachie H, Parr JR, Glod M et al. . Systematic review of tools to measure outcomes for young children with autism spectrum disorder. Health Technol Assess 2015;19:1–506. 10.3310/hta19410

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe