Background

Autistic children can have difficulty generalising treatment effects beyond the immediate treatment context. Paediatric Autism Communication Therapy (PACT) has been successful when delivered in the clinic. Here we tested the Paediatric Autism Communication Therapy-Generalised (PACT-G) intervention combined between home and education settings for its overall effect and mechanistic transmission of effect across contexts.

Methods

In this parallel, single-blind, randomised, controlled trial, we recruited autistic children aged 2–11 years in urban or semi-urban areas in Manchester, Newcastle, and London, England. Children needed to meet core autism criteria on Autism Diagnostic Observation Schedule-second edition (ADOS-2) and parent-rated Social Communication Questionnaire (SCQ-lifetime), and children older than 5 years were included if they had intentional communication but expressive language equivalent of age 4 years or younger. Eligible children were randomly assigned (1:1), using block randomisation (random block sizes of 2 and 4) and stratified for site, age (2–4 years vs 5–11 years), and gender, to either PACT-G plus treatment as usual or treatment as usual alone. Research assessors were masked to treatment allocation. The PACT-G intervention was delivered by a therapist in parallel to the child's parents at home and to learning-support assistants (LSA) at their place of education, using both in-person and remote sessions over a 6 month period, to optimise adult–child social interaction. Treatment as usual included any health support or intervention from education or local community services. The primary outcome was autism symptom severity using the ADOS-2, as measured by researchers, at 12 months versus baseline. Secondary outcomes were Brief Observation of Social Communication Change (BOSCC) and dyadic social interaction between child and adult across contexts, both at 12 months. Other secondary outcome measures were assessed using the following composites: language, anxiety, repetitive behaviour, adaptive behaviour, parental wellbeing, child health-related quality of life, and disruptive behaviour. Assessments were done at baseline, 7 months, and 12 months. We used an intention-to-treat (ITT) analysis of covariance for the efficacy outcome measures. Adverse events were assessed by researchers for all trial families at each contact and by therapists in the PACT-G group at each visit. This study is registered with the ISRCTN Registry, ISRCTN 25378536.

Findings

Between Jan 18, 2017, and April 19, 2018, 555 children were referred and 249 were eligible, agreed to participate, and were randomly assigned to either PACT-G (n=122) or treatment as usual (n=127). One child in the PACT-G group withdrew and requested their data be removed from the study, giving an ITT population of 248 children. 51 (21%) of 248 children were female, 197 (79%) were male, 149 (60%) were White, and the mean age was 4·0 years (SD 0·6). The groups were well balanced for demographic and clinical characteristics. In the PACT-G group, parents of children received a median of 10 (IQR 8–12) home sessions and LSAs received a median of 8 (IQR 5–10) education sessions over 6 months. We found no treatment effect on the ADOS-2 primary outcome compared with treatment as usual (effect size 0·04 [95% CI –0·19 to 0·26]; p=0·74), or researcher-assessed BOSCC (0·03 [–0·25 to 0·31]), language composite (–0·03 [–0·15 to 0·10]), repetitive behaviour composite (0·00 [–0·35 to 0·35]), adaptive behaviour composite (0·01 [–0·15 to 0·18]), or child wellbeing (0·09 [–0·15 to 0·34]). PACT-G treatment improved synchronous response in both parent (0·50 [0·36 to 0·65]) and LSA (0·33 [0·16 to 0·50]), mediating increased child communication with parent (0·26 [0·12 to 0·40]) and LSA (0·20 [0·06 to 0·34]). Child dyadic communication change mediated outcome symptom alteration on BOSCC at home (indirect effect –0·78 [SE 0·34; 95% CI –1·44 to –0·11]; p=0·022) although not in education (indirect effect –0·67 [SE 0·37; 95% CI –1·40 to 0·06]; p=0·073); such an effect was not seen on ADOS-2. Treatment with PACT-G also improved the parental wellbeing composite (0·44 [0·08 to 0·79]) and the child disruptive behaviour composite in home and education (0·29 [0·01 to 0·57]). Adverse events on child behaviour and wellbeing were recorded in 13 (10%) of 127 children in the treatment as usual group (of whom four [31%] were girls) and 11 (9%) of 122 in the PACT-G group (of whom three [33%] were girls). One serious adverse event on parental mental health was recorded in the PACT-G group and was possibly study related.

Interpretation

Although we found no effect on the primary outcome compared with treatment as usual, adaptation of the 12-month PACT intervention into briefer multicomponent delivery across home and education preserved the positive proximal outcomes, although smaller in effect size, and the original pattern of treatment mediation seen in clinic-delivered therapy, as well as improving parental wellbeing and child disruptive behaviours across home and school. Reasons for this reduced efficacy might be the reduced dose of each component, the effect of remote delivery, and the challenges of the delivery contexts. Caution is needed in assuming that changing delivery methods and context will preserve an original intervention efficacy for autistic children.

Funding

National Institute for Health Research and Medical Research Council Efficacy and Mechanism Evaluation Award.

中文翻译：

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英国幼儿自闭症儿童在家和教育中的综合社交沟通疗法 (PACT-G)：一项平行、单盲、随机对照试验

背景

自闭症儿童可能难以将治疗效果推广到直接治疗环境之外。小儿自闭症沟通疗法 (PACT) 在诊所交付时取得了成功。在这里，我们测试了在家庭和教育环境之间结合的小儿自闭症沟通治疗广义 (PACT-G) 干预的整体效果和跨环境的效果机制传递。

方法

在这项平行、单盲、随机、对照试验中，我们在英国曼彻斯特、纽卡斯尔和伦敦的城市或半城市地区招募了 2-11 岁的自闭症儿童。儿童需要满足自闭症诊断观察表第二版 (ADOS-2) 和家长评定的社会交流问卷（SCQ-终生）的核心自闭症标准，如果 5 岁以上的儿童有意向交流但表达语言相当，则包括在内4 岁或以下。符合条件的儿童被随机分配 (1:1)，使用块随机化（随机块大小为 2 和 4）并根据地点、年龄（2-4 岁vs5-11 岁）和性别，接受 PACT-G 加照常治疗或照常单独治疗。研究评估员对治疗分配不知情。PACT-G 干预由治疗师在家中与孩子的父母以及在他们教育地点的学习支持助理 (LSA) 并行进行，在 6 个月的时间内使用面对面和远程会议，以优化成人–儿童社会互动。照常治疗包括来自教育或当地社区服务的任何健康支持或干预。主要结果是研究人员在 12 个月时与基线相比使用 ADOS-2 测量的自闭症症状严重程度。次要成果是社会沟通变化的简要观察 (BOSCC) 和儿童与成人之间跨背景的二元社会互动，均在 12 个月时进行。使用以下复合材料评估其他次要结果指标：语言、焦虑、重复行为、适应行为、父母幸福感、儿童健康相关生活质量和破坏性行为。在基线、7 个月和 12 个月时进行评估。我们使用意向性治疗 (ITT) 协方差分析来衡量疗效结果。不良事件由研究人员在每次接触时对所有试验家庭进行评估，PACT-G 组的治疗师在每次访视时进行评估。本研究已在 ISRCTN 注册中心注册，ISRCTN 25378536。我们使用意向性治疗 (ITT) 协方差分析来衡量疗效结果。不良事件由研究人员在每次接触时对所有试验家庭进行评估，PACT-G 组的治疗师在每次访视时进行评估。本研究已在 ISRCTN 注册中心注册，ISRCTN 25378536。我们使用意向性治疗 (ITT) 协方差分析来衡量疗效结果。不良事件由研究人员在每次接触时对所有试验家庭进行评估，PACT-G 组的治疗师在每次访视时进行评估。本研究已在 ISRCTN 注册中心注册，ISRCTN 25378536。

发现

2017 年 1 月 18 日至 2018 年 4 月 19 日期间，转诊了 555 名儿童，其中 249 名符合条件并同意参加，并被随机分配到 PACT-G (n=122) 或照常治疗 (n=127)。PACT-G 组中的一名儿童退出并要求从研究中删除他们的数据，ITT 人群为 248 名儿童。248 名儿童中有 51 名 (21%) 为女性，197 名 (79%) 为男性，149 名 (60%) 为白人，平均年龄为 4·0 岁 (SD 0·6)。这些组在人口统计学和临床​​特征方面得到了很好的平衡。在 PACT-G 组中，孩子的父母在 6 个月内接受了 10 次（IQR 8-12）家庭课程的中位数，LSA 接受了 8 次（IQR 5-10）教育课程的中位数。与常规治疗相比，我们发现治疗对 ADOS-2 主要结局没有影响（效应大小 0·04 [95% CI –0·19 至 0·26]；p=0·74），或研究人员评估的 BOSCC（0·03 [–0·25 至 0·31]），语言综合（–0·03 [–0·15 至 0·10]），重复行为综合（0·00 [–0 ·35 至 0·35]），适应性行为综合（0·01 [–0·15 至 0·18]），或儿童幸福感（0·09 [–0·15 至 0·34]）。PACT-G 治疗改善了父母双方 (0·50 [0·36 至 0·65]) 和 LSA (0·33 [0·16 至 0·50]) 的同步反应，调节儿童与父母的沟通增加 (0· 26 [0·12 至 0·40]) 和 LSA (0·20 [0·06 至 0·34])。家庭 BOSCC 的儿童二元交流变化介导的结果症状改变（间接影响 –0·78 [SE 0·34；95% CI –1·44 至 –0·11]；p=0·022），尽管不在教育中（间接影响 –0·67 [SE 0·37；95% CI –1·40 至 0·06]；p=0·073）；在 ADOS-2 上没有看到这样的效果。PACT-G 治疗还改善了父母幸福感综合指数 (0·44 [0·08 至 0·79]) 和儿童在家庭和教育中的破坏性行为综合指数 (0·29 [0·01 至 0·57])。常规治疗组 127 名儿童中的 13 名（10%）（其中 4 名 [31%] 是女孩）和 PACT-G 组 122 名儿童中的 11 名（9%）记录了儿童行为和健康方面的不良事件（其中三名 [33%] 是女孩）。PACT-G 组记录了一项对父母心理健康的严重不良事件，可能与研究相关。

解释

虽然我们发现与常规治疗相比对主要结果没有影响，但将 12 个月的 PACT 干预调整为更短的家庭和教育多组分交付，保留了积极的近端结果，尽管效应量较小，并且治疗调解的原始模式见于诊所提供的治疗，以及改善父母的幸福感和儿童在家庭和学校的破坏性行为。功效降低的原因可能是每个成分的剂量减少、远程交付的影响以及交付环境的挑战。假设改变交付方法和环境将保持对自闭症儿童的原始干预效果，需要谨慎。

资金

美国国立卫生研究院和医学研究委员会功效和机制评估奖。