Long-Term Symptom Reduction Following the Preschool Autism Treatment Trial RCT (PACT)

Thursday, May 11, 2017: 2:40 PM
Yerba Buena 8 (Marriott Marquis Hotel)
J. Green1, A. Pickles2, T. Charman3, A. Le Couteur4, K. Leadbitter5, E. Salomone6, R. Cole Fletcher7, H. Tobin8, I. Gammer9, J. Lowry10, G. Vamvakas11, S. Byford12, C. R. Aldred8, V. Slonims13, H. McConachie14, P. Howlin15 and J. Parr16, (1)University of Manchester, Manchester, United Kingdom, (2)King's College London, London, UNITED KINGDOM, (3)Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom, (4)Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle Upon Tyne, UNITED KINGDOM, (5)University of Manchester, Manchester, United Kingdom of Great Britain and Northern Ireland, (6)Institute of Psychiatry, London, UNITED KINGDOM, (7)University of Durham, Durham, United Kingdom, (8)University of Manchester, Manchester, UNITED KINGDOM, (9)Institute of Psychiatry, King's College London, London, UNITED KINGDOM, (10)Newcastle University, IHS, Newcastle Upon Tyne, UNITED KINGDOM, (11)Kings College London, London, United Kingdom, (12)Kings College, London, UNITED KINGDOM, (13)Evelina Children's Hospital Guy's and St Thomas' NHS Foundation Trust, London, UNITED KINGDOM, (14)Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom, (15)King's College London, Institute of Psychiatry, London, UNITED KINGDOM, (16)Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, United Kingdom
Background:  It is not known whether early intervention can improve long-term autism symptom outcome.

Objectives:  To determine long-term outcomes of the Preschool Autism Communication Trial (PACT). We hypothesised enhanced intervention effect on autism symptom outcomes, and continuation of effects on parent and child social interaction.

Methods:  PACT tested a 12-month parent-mediated social communication intervention for children aged 2 - 4 years with severe autism (18 therapist-parent video-aided sessions and daily parent home-practice), randomized 1:1 against Treatment as Usual. We undertook follow-up ascertainment at all original trial sites (Manchester, Newcastle, and London, UK) at median 5·75 years (IQR 5·42–5·92) from the original trial endpoint. Pre-specified blinded primary outcomes were the Autism Diagnostic Observation Schedule Combined Severity Score (ADOS CSS); proportion of child dyadic initiatiations with parent from the Dyadic Communication Assessment Measure for Autism (DCMA), and an expressive-receptive language composite. Secondary outcomes included non-blinded parent-ratings of autism symptoms (SCQ), repetitive behaviours (RBQ), adaptive behavior (Vineland), and peer relationships (SDQ); teacher-ratings of adaptive behavior (Vineland). All analyses were by intention-to-treat. Study registration ISRCTN 58133827; funding UK Medical Research Council.

Results:  121 (80%) of the 152 trial participants (59 [77%] of 77 assigned to PACT intervention vs 62 [83%] of 75 assigned to treatment as usual) were traced and consented to be assessed. Mean age at follow-up was 10·5 years (SD 0·8). Group difference in favour of PACT on ADOS CSS was logodds effect size (ES) 0·64 (95% CI 0·07 to 1·20) at treatment endpoint and ES 0·70 (95% CI –0·05 to 1·47) at follow-up, giving a significant overall reduction in symptom severity over the course of the whole trial and follow-up period (ES 0·55, 95% CI 0·14 to 0·91, p=0·004; Figs 1 and 2). Figure 2 shows group time paths in relation to baseline (left) and TAU (right). DCMA child initiations at follow-up showed a Cohen’s d ES of 0·29 (95% CI –0.02 to 0.57) in favour of PACT and was significant over the course of the study (ES 0·33, 95% CI 0·11 to 0·57, p=0·004). Non-blind parent-rated autism symptoms (ES 0·40, 95% CI 0·05, 0·77) and repetitive behaviours (ES 0·87, 95% CI 0·47, 1·35) showed comparable treatment effects (Fig 1). There were no group differences in the language composite (ES 0·15, 95% CI –0·23 to 0·53) or comorbid mental health problems.

Conclusions:  This study supports the clinical value of the PACT intervention. It advances previous work by showing for the first time that a theoretically derived, developmentally targeted early intervention can have a sustained effect on autism symptom outcomes nearly 6 years after the end of treatment in a randomised trial. Such a sustained effect after time-limited intervention has implications for developmental theory and further research is needed to elucidate the developmental mechanisms. Strengths are the pre-specified ITT analysis on standard blinded outcomes and nearly 80% follow-up of one of the largest autism treatment cohorts. We cannot be sure how the results would generalized to milder autism spectrum disorder.