Exploring critical intervention features and trial processes in the evaluation of sensory integration therapy for autistic children.

BACKGROUND: We evaluated the clinical and cost-effectiveness of manualised sensory integration therapy (SIT) for autistic children with sensory processing difficulties in a two-arm randomised controlled trial. Trial processes and contextual factors which may have affected intervention outcomes were explored within a nested process evaluation. This paper details the process evaluation methods and results. We also discuss implications for evaluation of individual level, tailored interventions in similar populations. METHODS: The process evaluation was conducted in line with Medical Research Council guidance. Recruitment, demographics, retention, adherence, and adverse effects are reported using descriptive statistics. Fidelity of intervention delivery is reported according to the intervention scoring manual. Qualitative interviews with therapists and carers were undertaken to explore the acceptability of the intervention and trial processes. Qualitative interviews with carers explored potential contamination. RESULTS: Recruitment, reach and retention within the trial met expected thresholds. One hundred thirty-eight children and carers were recruited (92% of those screened and 53.5% of those who expressed an interest) with 77.5% retained at 6 months and 69.9% at 12 months post-randomisation. The intervention was delivered with structural and process fidelity with the majority (78.3%) receiving a 'sufficient dose' of intervention. However, there was considerable individual variability in the receipt of sessions. Carers and therapists reported that trial processes were generally acceptable though logistical challenges such as appointment times, travel and COVID restrictions were frequent barriers to receiving the intervention. No adverse effects were reported. CONCLUSIONS: The process evaluation was highly valuable in identifying contextual factors that could impact the effectiveness of this individualised intervention. Rigorous evaluations of interventions for autistic children are important, especially given the limitations such as limited sample sizes and short-term follow-up as faced by previous research. One of the challenges lies in the variability of outcomes considered important by caregivers, as each autistic child faces unique challenges. It is crucial to consider the role of parents or other caregivers in facilitating access to these interventions and how this may impact effectiveness. TRIAL REGISTRATION: This trial is registered as ISRCTN14716440. August 11, 2016.

Pragmatic randomised controlled trial of guided self-help versus individual cognitive behavioural therapy with a trauma focus for post-traumatic stress disorder (RAPID).

Background: Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. Objective: To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. Design: Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. Setting: Primary and secondary mental health settings across the United Kingdom's National Health Service. Participants: One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. Interventions: Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60-90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. Main outcome measures: Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. Results: Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI -∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval -∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years -0.04 (95% confidence interval -0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. Limitations: The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. Conclusions: Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. Future work: Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. Trial registration: This trial is registered as ISRCTN13697710. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.

Post-traumatic stress disorder is a common, disabling condition that can occur following major traumatic events. Typical symptoms include distressing reliving, avoidance of reminders and feeling a current sense of threat. First-choice treatments for post-traumatic stress disorder are individual, face-to-face talking treatments, of 12­16 hours duration, including cognitive behavioural therapy with a trauma focus. If equally effective treatments could be developed that take less time and can be largely undertaken in a flexible manner at home, this would improve accessibility, reduce waiting times and hence the burden of disease. RAPID was a randomised controlled trial using a web-based programme called Spring. The aim was to determine if trauma-focused guided self-help provided a faster and cheaper treatment for post-traumatic stress disorder than first-choice face-to-face therapy, while being equally effective. Guided self-help using Spring is delivered through eight steps. A therapist provides a 1-hour introductory meeting followed by four further, fortnightly sessions of 30 minutes each and four brief (around 5 minutes) telephone calls or e-mail contacts between sessions. At each session, the therapist reviews progress and guides the client through the programme, offering continued support, monitoring, motivation and problem-solving. One hundred and ninety-six people with post-traumatic stress disorder to a single traumatic event took part in the study. Guided self-help using Spring was found to be equally effective to first-choice face-to-face therapy at reducing post-traumatic stress disorder symptoms at 16 weeks. Very noticeable improvements were maintained at 52 weeks post-randomisation in both groups, when most results were inconclusive but in favour of face-to-face therapy. Guided self-help using Spring was significantly cheaper to deliver and appeared to be well-tolerated. It is noteworthy that not everyone benefitted from guided self-help using Spring, highlighting the importance of considering it on a person-by-person basis, and personalising interventions. But, the RAPID trial has demonstrated that guided self-help using Spring provides a low-intensity treatment option for people with post-traumatic stress disorder that is ready to be implemented in the National Health Service.

Further development and feasibility randomised controlled trial of a digital programme for adolescent depression, MoodHwb: study protocol.

INTRODUCTION: A digital programme, MoodHwb, was codesigned with young people experiencing or at high risk of depression, parents/carers and professionals, to provide support for young people with their mood and well-being. A preliminary evaluation study provided support for the programme theory and found that MoodHwb was acceptable to use. This study aims to refine the programme based on user feedback, and to assess the acceptability and feasibility of the updated version and study methods. METHODS AND ANALYSIS: Initially, this study will refine MoodHwb with the involvement of young people, including in a pretrial acceptability phase. This will be followed by a multicentre feasibility randomised controlled trial comparing MoodHwb plus usual care with a digital information pack plus usual care. Up to 120 young people aged 13-19 years with symptoms of depression and their parents/carers will be recruited through schools, mental health services, youth services, charities and voluntary self-referral in Wales and Scotland. The primary outcomes are the feasibility and acceptability of the MoodHwb programme (including usage, design and content) and of trial methods (including recruitment and retention rates), assessed 2 months postrandomisation. Secondary outcomes include potential impact on domains including depression knowledge and stigma, help-seeking, well-being and depression and anxiety symptoms measured at 2 months postrandomisation. ETHICS AND DISSEMINATION: The pretrial acceptability phase was approved by the Cardiff University School of Medicine Research Ethics Committee (REC) and the University of Glasgow College of Medicine, Veterinary and Life Sciences REC. The trial was approved by Wales NHS REC 3 (21/WA/0205), the Health Research Authority(HRA), Health and Care Research Wales (HCRW), university health board Research and Development (R&D) departments in Wales, and schools in Wales and Scotland. Findings will be disseminated in peer-reviewed open-access journals, at conferences and meetings, and online to academic, clinical, and educational audiences and the wider public. TRIAL REGISTRATION NUMBER: ISRCTN12437531.

Physical activity and exercise outcomes in Huntington's disease (PACE-HD): results of a 12-month trial-within-cohort feasibility study of a physical activity intervention in people with Huntington's disease.

INTRODUCTION: While physical activity (PA) is recognized as important in Huntington's disease (HD) disease management, there has been no long-term evaluation undertaken. We aimed to evaluate the feasibility of a nested (within cohort) randomized controlled trial (RCT) of a physical therapist-led PA intervention. METHODS: Participants were recruited from six HD specialist centers participating in the Enroll-HD cohort study in Germany, Spain and U.S. Assessments were completed at baseline and 12 months and linked to Enroll-HD cohort data. Participants at three sites (cohort) received no contact between baseline and 12 month assessments. Participants at three additional sites (RCT) were randomized to PA intervention or control group. The intervention consisted of 18 sessions delivered over 12 months; control group participants received no intervention, however both groups completed monthly exercise/falls diaries and 6-month assessments. RESULTS: 274 participants were screened, 204 met inclusion criteria and 116 were enrolled (59 in cohort; 57 in RCT). Retention rates at 12-months were 84.7% (cohort) and 79.0% (RCT). Data completeness at baseline ranged from 42.3 to 100% and at 12-months 19.2-85.2%. In the RCT, there was 80.5% adherence, high intervention fidelity, and similar adverse events between groups. There were differences in fitness, walking endurance and self-reported PA at 12 months favoring the intervention group, with data completeness >60%. Participants in the cohort had motor and functional decline at rates comparable to previous studies. CONCLUSION: Predefined progression criteria indicating feasibility were met. PACE-HD lays the groundwork for a future, fully-powered within cohort trial, but approaches to ensure data completeness must be considered. CLINICALTRIALS: GOV: NCT03344601.

Guided, internet based, cognitive behavioural therapy for post-traumatic stress disorder: pragmatic, multicentre, randomised controlled non-inferiority trial (RAPID).

OBJECTIVE: To determine if guided internet based cognitive behavioural therapy with a trauma focus (CBT-TF) is non-inferior to individual face-to-face CBT-TF for mild to moderate post-traumatic stress disorder (PTSD) to one traumatic event. DESIGN: Pragmatic, multicentre, randomised controlled non-inferiority trial (RAPID). SETTING: Primary and secondary mental health settings across the UK's NHS. PARTICIPANTS: 196 adults with a primary diagnosis of mild to moderate PTSD were randomised in a 1:1 ratio to one of two interventions, with 82% retention at 16 weeks and 71% retention at 52 weeks. 19 participants and 10 therapists were purposively sampled and interviewed for evaluation of the process. INTERVENTIONS: Up to 12 face-to-face, manual based, individual CBT-TF sessions, each lasting 60-90 minutes; or guided internet based CBT-TF with an eight step online programme, with up to three hours of contact with a therapist and four brief telephone calls or email contacts between sessions. MAIN OUTCOME MEASURES: Primary outcome was the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at 16 weeks after randomisation (diagnosis of PTSD based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, DSM-5). Secondary outcomes included severity of PTSD symptoms at 52 weeks, and functioning, symptoms of depression and anxiety, use of alcohol, and perceived social support at 16 and 52 weeks after randomisation. RESULTS: Non-inferiority was found at the primary endpoint of 16 weeks on the CAPS-5 (mean difference 1.01, one sided 95% confidence interval -∞ to 3.90, non-inferiority P=0.012). Improvements in CAPS-5 score of more than 60% in the two groups were maintained at 52 weeks, but the non-inferiority results were inconclusive in favour of face-to-face CBT-TF at this time point (3.20, -∞ to 6.00, P=0.15). Guided internet based CBT-TF was significantly (P<0.001) cheaper than face-to-face CBT-TF and seemed to be acceptable and well tolerated by participants. The main themes of the qualitative analysis were facilitators and barriers to engagement with guided internet based CBT-TF, treatment outcomes, and considerations for its future implementation. CONCLUSIONS: Guided internet based CBT-TF for mild to moderate PTSD to one traumatic event was non-inferior to individual face-to-face CBT-TF and should be considered a first line treatment for people with this condition. TRIAL REGISTRATION: ISRCTN13697710.

Sensory integration therapy for children with autism and sensory processing difficulties: the SenITA RCT.

BACKGROUND: Carers report unmet need for occupational therapy services addressing sensory difficulties in autism, yet insufficient evidence exists to recommend a therapeutic approach. OBJECTIVES: Our aim was to determine the clinical effectiveness and cost-effectiveness of sensory integration therapy for children with autism and sensory difficulties across behavioural, functional and quality-of-life outcomes. DESIGN: We carried out a parallel-group randomised controlled trial, incorporating an internal pilot and a process evaluation. Randomisation utilised random permuted blocks. SETTING AND PARTICIPANTS: Children were recruited via services and self-referral in Wales and England. Inclusion criteria were having an autism diagnosis, being in mainstream primary education and having definite/probable sensory processing difficulties. Exclusion criteria were having current/previous sensory integration therapy and current applied behaviour analysis therapy. INTERVENTION: The intervention was manualised sensory integration therapy delivered over 26 weeks and the comparator was usual care. OUTCOMES: The primary outcome was problem behaviours (determined using the Aberrant Behavior Checklist), including irritability/agitation, at 6 months. Secondary outcomes were adaptive behaviour, functioning and socialisation (using the Vineland Adaptive Behavior Scales); carer stress (measured using the Autism Parenting Stress Index); quality of life (measured using the EuroQol-5 Dimensions and Carer Quality of Life); functional change (according to the Canadian Occupational Performance Measure); sensory processing (determined using the Sensory Processing Measure™ at screening and at 6 months to examine mediation effects); and cost-effectiveness (assessed using the Client Service Receipt Inventory). Every effort was made to ensure that outcome assessors were blind to allocation. RESULTS: A total of 138 participants were randomised (n = 69 per group). Usual care was significantly different from the intervention, which was delivered with good fidelity and adherence and minimal contamination, and was associated with no adverse effects. Trial procedures and outcome measures were acceptable. Carers and therapists reported improvement in daily functioning. The primary analysis included 106 participants. There were no significant main effects of the intervention at 6 or 12 months. The adjusted mean difference between groups on the Aberrant Behavior Checklist - irritability at 6 months post randomisation was 0.40 (95% confidence interval -2.33 to 3.14; p = 0.77). Subgroup differences in irritability/agitation at 6 months were observed for sex of child (intervention × female = 6.42, 95% confidence interval 0.00 to 12.85; p = 0.050) and attention deficit hyperactivity disorder (intervention × attention deficit hyperactivity disorder = -6.77, 95% confidence interval -13.55 to -0.01; p = 0.050). There was an effect on carer stress at 6 months by region (intervention × South England = 7.01, 95% confidence interval 0.45 to 13.56; p = 0.04) and other neurodevelopmental/genetic conditions (intervention × neurodevelopmental/genetic condition = -9.53, 95% confidence interval -18.08 to -0.98; p = 0.030). Carer-rated goal performance and satisfaction increased across sessions (p < 0.001), with a mean change of 2.75 (95% confidence interval 2.14 to 3.37) for performance and a mean change of 3.34 (95% confidence interval 2.63 to 4.40) for satisfaction. Health economic evaluation suggests that sensory integration therapy is not cost-effective compared with usual care alone. LIMITATIONS: Limitations included variability of the intervention setting (i.e. NHS vs. private), delay for some receiving therapy, an error in administration of Vineland Adaptive Behavior Scales and no measurement of comparator arm goal performance. CONCLUSIONS: The intervention did not demonstrate clinical benefit above standard care. Subgroup effects are hypothesis-generating only. The intervention is likely to be effective for individualised performance goals, although it is unclear whether effects were in addition to standard care or were maintained. FUTURE WORK: Further investigation of subgroup effects is needed. TRIAL REGISTRATION: This trial is registered as ISRCTN14716440. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 29. See the NIHR Journals Library website for further project information.

Children with autism often experience problems with processing sensory information (e.g. noise, touch, movement, taste and sight), and this can lead to problems in daily life. This study was designed to see if sensory integration therapy can help children with these difficulties. Sensory integration therapy is a type of face-to-face play-based treatment that is delivered by occupational therapists. We compared sensory integration therapy with the type of treatment normally offered to children with autism (i.e. 'usual care'). We recruited children and their carers from Wales and England. Children could take part in the study if they had an autism diagnosis, had sensory processing difficulties and were in mainstream primary education. The children taking part in the study were randomly split into two groups. Sixty-nine children were given sensory integration therapy and 69 children carried on with their usual care. The sensory integration therapy involved 24 face-to-face sessions in an occupational therapy clinic, followed by two telephone calls with the carer. The sensory integration therapy lasted for 26 weeks. We collected information on the type of care being given to children in the usual-care group. Carers of each child were asked questions about their child's behaviour 6 and 12 months after starting the study. Some carers also completed an interview to talk about what it was like taking part in the study. Therapists delivered the sensory integration therapy well. Carers and therapists said that they saw some improvements. However, sensory integration therapy was not significantly better than the usual care and is a more expensive option. We cannot say that sensory integration therapy is helpful for all children with autism and different sensory processing difficulties; however, it might be helpful for some children to focus on specific problems. Future work could focus on which children and problems it would help the most.

Understanding the support experiences of families of children with autism and sensory processing difficulties: A qualitative study.

BACKGROUND: Support, such as information, advice and therapies, can play a vital role in the lives of families of autistic children. However, little is known about the support experiences of UK parents and carers. AIM: To explore experiences of and access to support for families of children with autism and sensory processing difficulties, from the perspective of parents and carers. METHODS: Semi-structured, timeline-assisted interviews were conducted with parents/carers of 30 children aged 5-11, exploring experiences of support. Framework analysis was used to identify themes in the interview data. RESULTS: Support varied widely and was not accessed equitably. Specialist autism support, together with support from other parents and voluntary organizations, was perceived as more useful than statutory and nonspecialist provision. Unmet support needs included an ongoing point of contact for information and advice for parents, and access to direct therapy and specialist mental health provision for children. CONCLUSIONS: Findings emphasize the need for a clear pathway of support following autism diagnosis, autism-specific training for professional service providers and specialist provision tailored to the needs of autistic children. PATIENT OR PUBLIC CONTRIBUTION: An advisory group of four parents of children with autism provided feedback on study procedures and materials, including participant information sheets and timeline completion instructions.

Can wearable technology be used to approximate cardiopulmonary exercise testing metrics?

BACKGROUND: Consumer wrist-worn wearable activity monitors are widely available, low cost and are able to provide a direct measurement of several markers of physical activity. Despite this, there is limited data on their use in perioperative risk prediction. We explored whether these wearables could accurately approximate metrics (anaerobic threshold, peak oxygen uptake and peak work) derived using formalised cardiopulmonary exercise testing (CPET) in patients undergoing high-risk surgery. METHODS: Patients scheduled for major elective intra-abdominal surgery and undergoing CPET were included. Physical activity levels were estimated through direct measures (step count, floors climbed and total distance travelled) obtained through continuous wear of a wrist worn activity monitor (Garmin Vivosmart HR+) for 7 days prior to surgery and self-report through completion of the short International Physical Activity Questionnaire (IPAQ). Correlations and receiver operating characteristic (ROC) curve analysis explored the relationships between parameters provided by CPET and physical activity. DEVICE SELECTION: Our choice of consumer wearable device was made to maximise feasibility outcomes for this study. The Garmin Vivosmart HR+ had the longest battery life and best waterproof characteristics of the available low-cost devices. RESULTS: Of 55 patients invited to participate, 49 (mean age 65.3 ± 13.6 years; 32 males) were enrolled; 37 provided complete wearable data for analyses and 36 patients provided full IPAQ data. Floors climbed, total steps and total travelled as measured by the wearable device all showed moderate correlation with CPET parameters of peak oxygen uptake (peak VO2) (R = 0.57 (CI 0.29-0.76), R = 0.59 (CI 0.31-0.77) and R = 0.62 (CI 0.35-0.79) respectively), anaerobic threshold (R = 0.37 (CI 0.01-0.64), R = 0.39 (CI 0.04-0.66) and R = 0.42 (CI 0.07-0.68) respectively) and peak work (R = 0.56 (CI 0.27-0.75), R = 0.48 (CI 0.17-0.70) and R = 0.50 (CI 0.2-0.72) respectively). Receiver operator curve (ROC) analysis for direct and self-reported measures of 7-day physical activity could accurately approximate the ventilatory equivalent for carbon dioxide (VE/VCO2) and the anaerobic threshold. The area under these curves was 0.89 for VE/VCO2 and 0.91 for the anaerobic threshold. For peak VO2 and peak work, models fitted using just the wearable data were 0.93 for peak VO2 and 1.00 for peak work. CONCLUSIONS: Data recorded by the wearable device was able to consistently approximate CPET results, both with and without the addition of patient reported activity measures via IPAQ scores. This highlights the potential utility of wearable devices in formal assessment of physical functioning and suggests they could play a larger role in pre-operative risk assessment. ETHICS: This study entitled "uSing wearable TEchnology to Predict perioperative high-riSk patient outcomes (STEPS)" gained favourable ethical opinion on 24 January 2017 from the Welsh Research Ethics Committee 3 reference number 17/WA/0006. It was registered on ClinicalTrials.gov with identifier NCT03328039.

Physical Activity and Exercise Outcomes in Huntington Disease (PACE-HD): Protocol for a 12-Month Trial Within Cohort Evaluation of a Physical Activity Intervention in People With Huntington Disease.

BACKGROUND: Exercise is emerging as an important aspect in the management of disease-related symptoms and functional decline in people with Huntington disease (HD). Long-term evaluation of physical activity and exercise participation in HD has yet to be undertaken. OBJECTIVE: The objective is to investigate the feasibility of a nested randomized controlled trial (RCT) alongside a longitudinal observational study of physical activity and exercise outcomes in people with HD. DESIGN: This will be a 12-month longitudinal observational study (n = 120) with a nested evaluation of a physical activity intervention (n = 30) compared with usual activity (n = 30) using a "trial within a cohort" design. SETTING: The study will take place in HD specialist clinics in Germany, Spain, and the United States, with intervention delivery in community settings. PARTICIPANTS: The participants will have early-mid-stage HD and be participating in the Enroll-HD study. INTERVENTION: This will be a 12-month physical activity behavioral change intervention, delivered by physical therapists in 18 sessions, targeting uptake of aerobic exercise and increased physical activity. MEASUREMENTS: All participants (n = 120) will complete Enroll-HD assessments (motor, cognitive, behavioral, and quality of life) at baseline and at 12 months. Additional Physical ACtivity and Exercise Outcomes in Huntington Disease (PACE-HD) assessments include fitness (predicted maximal oxygen uptake [V o2max]), self-reported and quantitative measures of physical activity, disease-specific symptoms, and walking endurance. RCT participants (n = 60) will complete an additional battery of quantitative motor assessments and a 6-month interim assessment. Enroll-HD data will be linked to PACE-HD physical activity and fitness data. LIMITATIONS: The limitations include that the embedded RCT is open, and assessors at RCT sites are not blinded to participant allocation. CONCLUSION: PACE-HD will enable determination of the feasibility of long-term physical activity interventions in people with HD. The novel "trial within a cohort" design and incorporation of data linkage have potential to reduce participant burden. This design could be applied to other neurological diseases and movement disorders where recruitment and retention are challenging.

Sensory integration therapy versus usual care for sensory processing difficulties in autism spectrum disorder in children: study protocol for a pragmatic randomised controlled trial.

BACKGROUND: Autism spectrum disorder (ASD) is a common lifelong condition affecting 1 in 100 people. ASD affects how a person relates to others and the world around them. Difficulty responding to sensory information (noise, touch, movement, taste, sight) is common, and might include feeling overwhelmed or distressed by loud or constant low-level noise (e.g. in the classroom). Affected children may also show little or no response to these sensory cues. These 'sensory processing difficulties' are associated with behaviour and socialisation problems, and affect education, relationships, and participation in daily life. Sensory integration therapy (SIT) is a face-to-face therapy or treatment provided by trained occupational therapists who use play-based sensory-motor activities and the just-right challenge to influence the way the child responds to sensation, reducing distress, and improving motor skills, adaptive responses, concentration, and interaction with others. With limited research into SIT, this protocol describes in detail how the intervention will be defined and evaluated. METHODS: This is a two-arm pragmatic individually 1:1 randomised controlled trial with an internal pilot of SIT versus usual care for primary school aged children (aged 4 to 11 years) with ASD and sensory processing difficulties; 216 children will be recruited from multiple sources. Therapy will be delivered in clinics meeting full fidelity criteria for manualised SIT over 26 weeks (face-to-face sessions: two per week for 10 weeks, two per month for 2 months; telephone call: one per month for 2 months). Follow-up assessments will be completed at 6 and 12 months post-randomisation. Prior to recruitment, therapists will be invited to participate in focus groups/interviews to explore what is delivered as usual care in trial regions; carers will be invited to complete an online survey to map out their experience of services. Following recruitment, carers will be given diaries to record their contact with services. Following intervention, carer and therapist interviews will be completed. DISCUSSION: Results of this trial will provide high-quality evidence on the clinical and cost effectiveness of SIT aimed at improving behavioural, functional, social, educational, and well-being outcomes for children and well-being outcomes for carers and families. TRIAL REGISTRATION: ISRCTN14716440 . Registered on 8 November 2016.