Effect of Preemptive Intervention on Developmental Outcomes Among Infants Showing Early Signs of Autism: A Randomized Clinical Trial of Outcomes to Diagnosis
Authors: Daniel Blenkley
Stefanie Dimov
Jane Doyle
Leonie Segal
Vicky Slonims
Gail A Alvares
Michelle Renton
John Wray
Sarah Pillar
Jodie Smith
Cheryl Dissanayake
Teresa Iacono
Emma Davidson
Catherine A Bent
Matthew N Cooper
Maryam Boutrus
Abby Chee
Carol Taylor
Alena Clark
Megan Harrap
Nancy Sadka
Lacey Chetcuti
Andrew J O Whitehouse
Jonathan Green
Wesley Billingham
Kristelle Hudry
Scott Wakeling
Cherie C Green
Daniel F Pope
Murray Maybery
Lisa Matys
Kandice J Varcin
Ming Wai Wan
Josephine Barbaro
Megan Grant
Catherine Rowbottam
Journal: JAMA Pediatrics (2021)
Discipline: CLINICAL MEDICINE
Keywords: Autism spectrum disorder; preemptive intervention; infants; diagnosis; randomized clinical trial
Affiliations: CliniKids, Telethon Kids Institute, Nedlands, Western Australia, Australia., University of Western Australia, Crawley, Western Australia, Australia., Cooperative Research Centre for Living with Autism, Long Pocket, Indooroopilly, Queensland, Australia., School of Allied Health Sciences, Griffith University, Gold Coast, Queensland, Australia., Olga Tennison Autism Research Centre, School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, Australia., Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, Australia., Perinatal Mental Health and Parenting Research Unit, Division of Psychology and Mental Health, School of Health Sciences, University of Manchester, Manchester, United Kingdom., School of Psychological Science, University of Western Australia, Crawley, Western Australia, Australia., Child and Adolescent Health Service, Child Development Service, West Perth, Western Australia, Australia., Living with Disability Research Centre, College of Science, Health, and Engineering, Victoria, Australia., Australian Centre for Precision Health, Allied Health and Human Movement, University of South Australia, South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, Australia., Children's Neurosciences, Evelina London Children's Hospital/Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, United Kingdom., Division of Neuroscience and Experimental Psychology, School of Biological Sciences, University of Manchester, Manchester, United Kingdom., Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Greater Manchester Mental Health NHS Trust, Manchester, United Kingdom.

Abstract:  Importance: Intervention for individuals with autism spectrum disorder (ASD) typically commences after diagnosis. No trial of an intervention administered to infants before diagnosis has shown an effect on diagnostic outcomes to date. Objective: To determine the efficacy of a preemptive intervention for ASD beginning during the prodromal period. Design, setting, and participants: This 2-site, single rater-blinded randomized clinical trial of a preemptive intervention vs usual care was conducted at 2 Australian research centers (Perth, Melbourne). Community sampling was used to recruit 104 infants aged 9 to 14 months showing early behaviors associated with later ASD, as measured by the Social Attention and Communication Surveillance-Revised. Recruitment occurred from June 9, 2016, to March 30, 2018. Final follow-up data were collected on April 15, 2020. Interventions: Infants were randomized on a 1:1 ratio to receive either a preemptive intervention plus usual care or usual care only over a 5-month period. The preemptive intervention group received a 10-session social communication intervention, iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care comprised services delivered by community clinicians. Main outcomes and measures: Infants were assessed at baseline (approximate age, 12 months), treatment end point (approximate age, 18 months), age 2 years, and age 3 years. Primary outcome was the combined blinded measure of ASD behavior severity (the Autism Observation Scale for Infants and the Autism Diagnostic Observation Schedule, second edition) across the 4 assessment points. Secondary outcomes were an independent blinded clinical ASD diagnosis at age 3 years and measures of child development. Analyses were preregistered and comprised 1-tailed tests with an α level of .05. Results: Of 171 infants assessed for eligibility, 104 were randomized; 50 infants (mean [SD] chronological age, 12.40 [1.93] months; 38 boys [76.0%]) received the iBASIS-VIPP preemptive intervention plus usual care (1 infant was excluded after randomization), and 53 infants (mean [SD] age, 12.38 [2.02] months; 32 boys [60.4%]) received usual care only. A total of 89 participants (45 in the iBASIS-VIPP group and 44 in the usual care group) were reassessed at age 3 years. The iBASIS-VIPP intervention led to a reduction in ASD symptom severity (area between curves, -5.53; 95% CI, -∞ to -0.28; P = .04). Reduced odds of ASD classification at age 3 years was found in the iBASIS-VIPP group (3 of 45 participants [6.7%]) vs the usual care group (9 of 44 participants [20.5%]; odds ratio, 0.18; 95% CI, 0-0.68; P = .02). Number needed to treat to reduce ASD classification was 7.2 participants. Improvements in caregiver responsiveness and language outcomes were also observed in the iBASIS-VIPP group. Conclusions and relevance: Receipt of a preemptive intervention for ASD from age 9 months among a sample of infants showing early signs of ASD led to reduced ASD symptom severity across early childhood and reduced the odds of an ASD diagnosis at age 3 years. Trial registration: http://anzctr.org.au identifier: ACTRN12616000819426. 

Retracted: No

PubPeer comments:
 This article was reviewed on the error bar podcast episode 19: https: theerrorbar.com ?e=19 story 86: https: theerrorbar.com ?s=86. The review was done in the light of newspaper headlines about the article. The slightly-edited transcript is copied here: headline: AUTISM IS TREATABLE tweet: a small intervention study in australia reports that 10 sessions of infant therapy can reduce the likelihood of developing autism by age three. in fact, all the statistics are weak and multiple uncorrected tests were done. ignore. description: The Week, a magazine that I read every, er, week, reported on the 2nd October that infants who display signs of autism are far less likely to later be diagnosed as autistic several years later if they receive ten sessions of social interaction therapy over five months. the effect of this remarkable therapy was that, at age 3 years, only 6.7 percent of the children receiving therapy were diagnosed with autism, while one in five of the control group were. evaluation: does therapy prevent autism? it might do, but the numbers of children involved in this study does not inspire confidence. autism refers to a range of developmental conditions that may affect around 1% of people. when media stories report figures like 6.7 percent of a population, we expect that there are at least 1000 people being studied - why else would they give us the percentage figures to the nearest tenth of a percent? in fact, this 6.7 percent is three children. the one in five figure is nine children. why doesn t The Week just say three and nine? is three very different from nine? well that depends on how many children were treated. in the paper, published in JAMA Paediatrics, they started with 104 children aged 9 to 14 months who displayed potential signs of autism. the children were divided into two groups of 52, half were given 10 sessions of social interaction therapy plus the usual care; the other half received just the usual care. assessments were carried out at 12, 18, 24 36 months of age. the authors main measure was the severity of autism symptoms, but they also looked at other factors, including whether children were classified as autistic or not. some children dropped out of the study, so the final sample was 45 children who had therapy 44 [sic] who had not. as a nerdy stats fan, three out of 45 nine out of 44 look to me like a weak effect of treatment. in the paper, the statistical tests they used were all one-tailed - that is, they were only looking for improvements in the treated group were happy to ignore any negative effects of therapy. not a good idea where children are concerned. indeed, if you do the more justifiable two-tailed tests, then there are no statistically significant improvements in the treated group. i also ran my own statistical test, dear listener. the humble chi-squared test, which sounds like a form of group meditation, is a simple way to test whether there is an association between a particular group of people a particular outcome. putting the numbers 42, 3, 35, 9 into the test gave me the following result... ... not significant. that s right - the far less likely reported by The Week was, in fact, not less likely when analysed over a cocktail at the error bar. looking across the paper as a whole, there were three assessment times, multiple outcome measures, no corrections for multiple comparisons a parade of unusually weak 1-tailed p-values which error bar nerds will enjoy: .04, .04, .02, .02, .02, .02. conclusion: autism is a collection of conditions that neuroscience psychology is, as yet, unable to explain or effectively intervene on. the importance of the topic makes clear that small, weak studies like this one should be ignored, for now. short conclusion: no, it doesn t ,