Dheeraj Rai’s research while affiliated with University of Bristol and other places

Background Research has demonstrated a strong relationship between autism and gender dysphoria (GD) and that this relationship could be explained by obsessional interests which are characteristic of autism. However, these studies often measured obsessions using either single items which questions the reliability of the findings, or within autistic trait measures meaning the findings may simply index a more general relationship between autistic traits and GD. Therefore, the present study aimed to investigate the relationships between obsessional thoughts and traits of GD using a measure of obsessional thoughts alongside a measure of autistic traits, which was investigated in both non-clinical and clinical samples. Methods A total of 145 non-clinical participants took part in Study 1 and all completed the Autism-Spectrum Quotient (AQ) as a measure of autistic traits, the Obsessive-Compulsive Inventory-Revised (OCI-R) obsessional thoughts subscale as a measure of obsessional thoughts, and the Gender-Identity/Gender-Dysphoria Questionnaire (GIDYQ) to measure traits of GD. For Study 2, a total of 226 participants took part in Study 2 and all completed the same measures as in Study 1. They included participants diagnosed with GD (N = 49), autism (N = 65), OCD (N = 46) and controls with no diagnosis (N = 66). Results The hierarchical linear regression for Study 1 showed that both total AQ and OCI-R obsessional thoughts scores were uniquely associated with GIDYQ scores, with no interaction effect between the scores. The results for Study 2, from a hierarchical linear regression, once again found that obsessional thoughts and autistic traits were each uniquely associated with GIDYQ scores, but not their interaction. The GD and autistic groups both reported significantly greater traits of GD than the OCD and control groups, with the GD group reporting higher scores than the autistic group. Limitations Participants self-reported their diagnoses for Study 2, but diagnostic tests to verify these were not administered. Traits of GD were also measured at a single point in time, despite such traits being transient and continuous. Conclusions The results show both obsessional thoughts and autistic traits are uniquely associated with GD, and that autistic people experience greater traits of GD than other clinical groups.

Background: Interventions for anxiety need to be adapted to meet the needs of autistic people with moderate to severe learning disabilities and successfully modelled before evidence about efficacy can be generated from clinical trials. Objectives: The objectives were to: (1) adapt a behavioural intervention for anxiety, develop an intervention fidelity checklist and logic model, and appraise candidate outcome measures, together with carers, autistic people, and clinicians, (2) characterise treatment-as-usual, (3) model the adapted intervention to determine the acceptability and feasibility for all stakeholders, judge the appropriateness of outcome measures, examine the feasibility and acceptability of consent and associated processes and (4) describe factors that facilitate or challenge intervention delivery. Design: This study had two phases. Phase 1a: using consensus methods, an intervention adaptation group was formed who met to adapt the intervention, appraise candidate outcome measures, and contribute to the development of the intervention fidelity checklists and logic model. Phase 1b: a national online survey was conducted with professionals to characterise treatment-as-usual. Phase 2: this was a single-group non-randomised feasibility study designed to model the intervention to test intervention feasibility and acceptability, outcome measures, and aspects of the research process. Setting: Participants were recruited from National Health Service community adult learning disabilities teams in England. Participants: Participants aged 16 and over with a diagnosis of autism, moderate to severe learning disabilities, an anxiety disorder, and a carer who was available to take part in the intervention. For those who lacked capacity to make a decision about taking part, a consultee had to provide advice that the participant should be included in the study. Interventions: The intervention comprised 12 sessions alongside treatment-as-usual. Main outcome measures: The feasibility and acceptability of the intervention and research processes, outcome measure completion rates, and intervention adherence. Results: The intervention was successfully adapted and modelled with 28 autistic participants with moderate to severe learning disabilities. The intervention was judged to be feasible and acceptable by autistic adults with learning disabilities, carers, and therapists. Carers and therapists suggested minor intervention revisions. Carers completed 100% of outcome measures and the missing data rate was low; however, they indicated that some of the questions were repetitive and said they had difficulty responding to some items. The use of the Mental Capacity Act, 2005, led to an average 5-week delay to participant enrolment. The accrual rate was affected by the COVID-19 pandemic and improved during the summer and early autumn of 2022. Limitations: Randomisation was not modelled within this feasibility study, although carers and therapists indicated that this would be acceptable. Conclusions: The BEAMS-ID intervention and associated study processes were judged to be feasible and acceptable. The intervention required minor revision. Future work: The BEAMS-ID intervention should be tested further within a trial. Study registration: This study is registered as ISRCTN12637590. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129804) and is published in full in Health Technology Assessment; Vol. 28, No. 72. See the NIHR Funding and Awards website for further award information.

Aims Adults with Down syndrome (DS) face significant health inequalities and are at increased risk of numerous health concerns. Despite the need, there is a lack of high-quality randomised trial evidence and clinical interventions for people with DS are largely based on consensus guidelines or clinician preferences. As life-expectancy of those with DS increases, the research gap continues to widen. There is a perception that randomised controlled trials (RCTs) involving people with DS may be hard to carry out due to difficulties in recruitment and retention of participants. However, there is no scientific literature exploring this topic. This systematic review aimed to assess planned vs actual recruitment and retention in RCTs involving adults with DS, and to summarise reported facilitators and barriers to participation of adults with DS in relevant trials. Methods The MEDLINE, PsycINFO, EMBASE databases were searched systematically to retrieve all RCTs involving adults with DS aged 16 years or older published from 01.11.1961 to 15.12.2023. Ongoing RCTs were identified from trial registries and searches were supplemented by review of reference lists. Data extraction is ongoing but seeks to elicit details of trial design; planned and achieved recruitment sample size; planned and achieved retention rate, and any specific recruitment or retention strategies described. Risk of bias analysis was not relevant to the research question and so not performed. The review was prospectively registered on Prospero (CRD42023447126). Results The database searches retrieved 1,825 results. Post deduplication, 1,518 articles underwent title and abstract screening, of which 82 full texts were reviewed. 53 papers were included in the final analysis, reflecting 47 RCTs involving 1,772 individuals. Commonly studied interventions included exercise programmes for physical fitness and pharmaceuticals that may augment neuropsychological function. Studies typically reported small sample sizes at the point of randomisation (mean = 38.5, SD = 49.6), with over half reporting a sample size of n < 50. A significant number of studies reported difficulty recruiting and retaining participants (detailed data will be available in the poster). Of the minority of articles that reported power calculations, several reported failure to meet target sample size. Conclusion Initial results point to a paucity of high-quality, large-scale RCTs involving adults with DS and challenges related to recruitment of participants. The results may aid development of strategies that allow clinical trial teams to overcome challenges in recruitment and retention in RCTs, and may eventually contribute to the improved health and wellbeing of adults with DS.

Background The aim of this feasibility study was to adapt and model a behavioural intervention for anxiety with autistic adults with moderate to severe intellectual disabilities. Method Twenty-eight autistic adults with moderate or severe intellectual disabilities, 37 carers, and 40 therapists took part in this single-group non-randomised feasibility study designed to test intervention feasibility and acceptability, outcome measures, and research processes. Results The intervention was judged as feasible and acceptable by autistic adults with intellectual disabilities, carers, and therapists. Minor intervention revisions were suggested. Carers completed 100% of outcome measures and the missing data rate was low. Complying with legislation governing the inclusion of participants who lack capacity to decide whether they wanted to take part in this study led to an average 5-week enrolment delay. Conclusion The intervention and associated study processes were judged to be feasible and acceptable and should now be tested within a larger randomised trial.

This systematic review investigated how studies have measured gender dysphoria (GD) in autistic samples and the impact of using different measures on study results. The literature search identified 339 relevant papers, with 12 of them meeting the inclusion criteria. Results showed that seven different measures of GD characteristics have been used with autistic samples and that the studies consistently reported a greater number of GD characteristics and a greater severity of GD in autistic compared to non-autistic samples. Methodological common practices were found in recruiting participants from clinical settings rather than the general population, having more autistic males than females in the samples, for studies being conducted in Europe, North America, and Oceania, and using single-item measures of GD for samples of autistic children. Issues were identified with study designs and measures of GD, suggesting a need for a more standardized multi-item self-report measure of GD for use in clinical and non-clinical samples across different ages and cultures.

The purpose of this study is to explore the views of autistic adults on randomised controlled trials, specifically on processes such as randomisation and blinding, to understand the barriers and facilitators for recruiting autistic people to randomised controlled trials involving medications. We conducted one-to-one interviews with 49 autistic adults. Interviews were audio-recorded and analysed thematically. The participants found randomised controlled trial processes acceptable and linked positive attitudes towards randomised controlled trial participation to autistic peoples’ heightened sense of fairness and preference for evidence-driven knowledge. However, randomised controlled trial designs may be incompatible with a (1) preference for a controlled predictable world, (2) perceived vulnerability at physical and mental health levels and (3) history of misunderstanding and exclusion, crucially from healthcare professionals. Suggestions that emerged from our findings include efforts to co-produce research to nurture trust and adapting communication practices to improve access to trials. Autistic people are a highly motivated group to work with research teams to mitigate barriers to randomised controlled trial participation. We explored what psychosocial determinants play a role in the acceptability of randomised controlled trials to test interventions to improve quality of life and mental health in autistic adults. The study provides useful information that may help the design and conduct of more accessible trials with and for the autistic community. Lay abstract Large randomised controlled trials are used to test healthcare treatments. Yet there are no large randomised controlled trials on effective treatments for common mental health issues affecting autistic adults. The purpose of this study was to learn what autistic adults think about randomised controlled trials in preparation for a randomised controlled trial testing a medication for anxiety. This means we wanted to know their opinions about the way randomised controlled trials are done, such as how people are chosen to be in the study and how the study is carried out. We did this by talking to 49 autistic adults individually and asking them questions. We found that most of the people we talked to were okay with the way randomised controlled trials are done. They thought it was fair and they liked that it was based on evidence. However, some autistic people might find it hard to take part in randomised controlled trials. Some people did not like the uncertainty of not knowing what treatment they would receive in a randomised controlled trial. Others felt too vulnerable and may have had bad experiences with healthcare in the past. We found that it is important to involve autistic people early on and at every stage when designing a clinical trial. Care about how clear and precise the study communication is will build trust and improve access to research. Our study indicates that it is possible to conduct large randomised controlled trials with and for autistic people. This can ultimately contribute to the improvement of healthcare outcomes for this population.

Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population is not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo, and to quantify any adverse effects. Methods: STRATA is a two parallel group, multi-centre, pragmatic, double blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥10 at screening will be randomised 1:1 to either 25mg sertraline or placebo, with subsequent flexible dose titration up to 200mg. The primary outcome is GAD-7 scores at 16-weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability, and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24- and 52-weeks post-randomisation, with brief safety checks and data collection at 1-2, 4, 8, 12 and 36 weeks. An economic evaluation to study cost-effectiveness of sertraline vs placebo, and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. Discussion: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration: ISRCTN, ISRCTN15984604. Registered 08 February 2021, https://www.isrctn.com/ISRCTN15984604. EudraCT: 2019-004312-66. ANZCTR,ACTRN12621000801819. Registered 07 April 2021.

Background: The COVID-19 pandemic resulted in large-scale public health restrictions and lockdowns across many countries. There is an increasing literature on the varied impact of such lockdowns in autistic adults. However, there is very little research on how the pandemic and related public health measures may impact the willingness of autistic people in engaging and taking part in research. The aim of this qualitative study was to explore autistic adults' experiences of the COVID-19 lockdown and how the pandemic may affect future research participation. Methods: We conducted in-depth interviews with 31 autistic adults between March and July 2020. Transcripts were analyzed thematically within a critical realism framework. Results: Participants identified positive aspects of lockdown such as enjoying the lack of social pressures and using their well-developed skills for dealing with uncertainty. Autistic people also shared challenges of adjusting to lockdown, for example, rapid change in daily routines. While hopeful about the freedom gained from easing restrictions, participants were concerned about the inconsistent communication and application of rules during the transition out of lockdown. This may have exacerbated already rising mental health issues among autistic people. The participants viewed research participation and engagement with increased relevance during the pandemic and welcomed efforts to conduct research using online methods of communication. Conclusion: The COVID-19 lockdown had a varied effect in the lives and routines of autistic people. However, health care providers and researchers need to be mindful of rising mental health issues in the aftermath of the pandemic, especially for people who were already vulnerable. The response to the pandemic may have offered opportunities for innovation in research processes enabling more autistic people to engage with research and making studies more inclusive.

The COVID-19 lockdown was a set of nationwide public health restrictions in force on the UK from March 2020 in response to the coronavirus pandemic. Co-occurring anxiety and depression in autistic people placed them at heightened risk of potential adverse mental health due to the lockdown. Furthermore, the impact of current and future public health measures on autistic people’s willingness to take part in autism research was unknown. We carried out in-depth interviews with 31 autistic adults exploring their experiences of the COVID-19 lockdown and how the pandemic may affect future research participation. Transcripts were analysed thematically within a critical realism framework. Participants identified positive aspects of lockdown such as enjoying the lack of social pressures and using their well-developed skills for dealing with uncertainty. Autistic people also shared challenges of adjusting to lockdown, e.g., rapid change in daily routines. While hopeful about the freedom gained from easing restrictions, participants were concerned about the inconsistent communication and application of rules during the transition out of lockdown which may exacerbate already rising mental health issues among autistic people. The participants viewed research participation and engagement with increased relevance during the pandemic and welcomed efforts to conduct research using online methods of communication. The COVID-19 lockdown had a varied effect in the lives and routines of autistic people. However, healthcare providers and researchers need to be mindful of rising mental health issues during the pandemic, especially for people who were already vulnerable. The response to the pandemic may have offered opportunities for innovation in research processes enabling more autistic people to engage with research and making studies more inclusive.

Low-intensity cognitive behaviour therapy including behavioural activation is an evidence-based treatment for depression, a condition frequently co-occurring with autism. The feasibility of adapting low-intensity cognitive behaviour therapy for depression to meet the needs of autistic adults via a randomised controlled trial was investigated. The adapted intervention (guided self-help) comprised materials for nine individual sessions with a low-intensity psychological therapist. Autistic adults (n = 70) with depression (Patient Health Questionnaire-9 score ⩾10) recruited from National Health Service adult autism services and research cohorts were randomly allocated to guided self-help or treatment as usual. Outcomes at 10-, 16- and 24-weeks post-randomisation were blind to treatment group. Rates of retention in the study differed by treatment group with more participants attending follow-up in the guided self-help group than treatment as usual. The adapted intervention was well-received, 86% (n = 30/35) of participants attended the pre-defined ‘dose’ of five sessions of treatment and 71% (25/35) attended all treatment sessions. The findings of this pilot randomised controlled trial indicate that low-intensity cognitive behaviour therapy informed by behavioural activation can be successfully adapted to meet the needs of autistic people. Evaluation of the effectiveness of this intervention in a full scale randomised controlled trial is now warranted.