title: Treatment mechanism in the MRC preschool autism communication trial: implications for study design and parent-focussed therapy for children.
abstract: BACKGROUND
  The PACT randomised-controlled trial evaluated a parent-mediated communication-focused treatment for children with autism, intended to reduce symptom severity as measured by a modified Autism Diagnostic Observation Schedule-Generic (ADOS-G) algorithm score. The therapy targeted parental behaviour, with no direct interaction between therapist and child. While nonsignificant group differences were found on ADOS-G score, significant group differences were found for both parent and child intermediate outcomes. This study aimed to better understand the mechanism by which the PACT treatment influenced changes in child behaviour though the targeted parent behaviour.
  
  
  METHODS
  Mediation analysis was used to assess the direct and indirect effects of treatment via parent behaviour on child behaviour and via child behaviour on ADOS-G score. Alternative mediation was explored to study whether the treatment effect acted as hypothesised or via another plausible pathway. Mediation models typically assume no unobserved confounding between mediator and outcome and no measurement error in the mediator. We show how to better exploit the information often available within a trial to begin to address these issues, examining scope for instrumental variable and measurement error models.
  
  
  RESULTS
  Estimates of mediation changed substantially when account was taken of the confounder effects of the baseline value of the mediator and of measurement error. Our best estimates that accounted for both suggested that the treatment effect on the ADOS-G score was very substantially mediated by parent synchrony and child initiations.
  
  
  CONCLUSIONS
  The results highlighted the value of repeated measurement of mediators during trials. The theoretical model underlying the PACT treatment was supported. However, the substantial fall-off in treatment effect highlighted both the need for additional data and for additional target behaviours for therapy.
authors.affiliation: Department of Biostatistics, Institute of Psychiatry, Kings College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pickles
authors.forename: Victoria
authors.initials: V
authors.lastname: Harris
authors.forename: Jonathan
authors.initials: J
authors.lastname: Green
authors.forename: Catherine
authors.initials: C
authors.lastname: Aldred
authors.forename: Helen
authors.initials: H
authors.lastname: McConachie
authors.forename: Vicky
authors.initials: V
authors.lastname: Slonims
authors.forename: Ann
authors.initials: A
authors.lastname: Le Couteur
authors.forename: Kristelle
authors.initials: K
authors.lastname: Hudry
authors.forename: Tony
authors.initials: T
authors.lastname: Charman
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis / Q000628:therapy*; D002675:Child, Preschool; D003142:Communication; D005260:Female; D006801:Humans; D008297:Male; D010287:Parent-Child Relations; D010290:Parents / Q000523:psychology*; D011615:Psychotherapy, Group / Q000379:methods*; D012107:Research Design / Q000592:standards*; D016037:Single-Blind Method; D016896:Treatment Outcome
keywords: Autism; measurement error; mediation; parent-child interaction; parent-focussed therapy