Estimating the lifetime costs and benefits of the Incredible Years Teacher Classroom Management intervention using data from 30 months follow up of the STARS Trial.

OBJECTIVES: The Incredible Years Teacher® Classroom Management (IY-TCM) intervention is associated with short-term improvements in mental health difficulties in young people. The aim was to estimate the long-term impact and cost-effectiveness of the IY-TCM intervention compared to no intervention. METHODS: An existing health economic model (LifeSim 1.0) was used to translate short-term changes in the Strength and difficulties questionnaire (SDQ), based on the STARS cluster randomised controlled trial of the IY-TCM intervention in schools, into estimated medium- and long-term effects using multiple longitudinal datasets. LifeSim 1.0 was adapted to incorporate teacher-reported SDQ and account for individual heterogeneity. Cost-effectiveness analyses were conducted using the trial-based intervention cost with subgroup analyses on deprivation, conduct scores and parental depression in the simulated baseline population. RESULTS: Regression analyses show significant predictor variables for intervention effectiveness including deprivation and baseline SDQ. LifeSim results indicate small gains in long-term outcomes, and cost-effective analyses estimated that the IY-TCM intervention could be cost-effective but there was a large amount of uncertainty (Net monetary benefit (NMB)=£10, Estimated CI = -£134, £156). Benefits and certainty of cost-effectiveness were greater, for some subgroups such as those with high conduct scores at baseline (NMB=£206, Estimated CI = £26, £318). CONCLUSIONS: IY-TCM could be cost-effective but there was a large amount of uncertainty around costs and benefits. Greater benefits for pupils with difficulties at baseline suggest that the intervention may be more cost-effective for schools in more deprived areas with high levels of conduct problems.

Clinical effectiveness of the psychological therapy Mental Health Intervention for Children with Epilepsy in addition to usual care compared with assessment-enhanced usual care alone: a multicentre, randomised controlled clinical trial in the UK.

BACKGROUND: Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aim was to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. METHODS: We conducted a parallel group, multicentre, open-label, randomised controlled trial of participants aged 3-18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomised (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behaviour therapy and behavioural parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analysed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomisation. The study is complete and registered with ISRCTN (57823197). FINDINGS: 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and Jan 31, 2022. Between Aug 28, 2019, and Feb 21, 2022, 334 participants (mean ages 10·5 years [SD 3·6] in the MICE group vs 10·3 [4·0] in control group at baseline) were randomly assigned to an intervention using minimisation balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. 168 (50%) of the participants were female and 166 (50%) were male. 166 participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17·6 (SD 6·3) and 19·6 (6·1) for the 148 participants in the control group. The adjusted effect of MICE was -1·7 (95% CI -2·8 to -0·5; p=0·0040; Cohen's d, 0·3). 14 (8%) patients in the MICE group experienced at least one serious adverse event compared with 24 (14%) in the control group. 68% percent of serious adverse events (50 events) were admission due to seizures. INTERPRETATION: MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioural difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilising an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serves as a model for other chronic health conditions in young people. FUNDING: UK National Institute for Health Research Programme Grants for Applied Research programme and Epilepsy Research UK Endeavour Project Grant.

A randomised controlled trial to investigate the clinical effectiveness and cost effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for depressed non-responders to Increasing Access to Psychological Therapies (IAPT) high-intensity therapies: study protocol.

BACKGROUND: Major depression represents a pressing challenge for health care. In England, Increasing Access to Psychological Therapies (IAPT) services provide evidence-based psychological therapies in a stepped-care approach to patients with depression. While introduction of these services has successfully increased access to therapy, estimates suggest that about 50% of depressed patients who have come to the end of the IAPT pathway still show significant levels of symptoms. This study will investigate whether Mindfulness-Based Cognitive Therapy (MBCT), a group intervention combining training in mindfulness meditation and elements from cognitive therapy, can have beneficial effects in depressed patients who have not responded to high-intensity therapy in IAPT. It will seek to establish the effectiveness and cost-effectiveness of MBCT as compared to the treatment these patients would usually receive. METHODS: In a 2-arm randomised controlled trial, patients who currently meet the criteria for major depressive disorder and who have not sufficiently responded to at least 12 sessions of IAPT high-intensity therapy will be allocated, at a ratio of 1:1, to receive either MBCT (in addition to treatment as usual [TAU]) or continue with TAU only. Assessments will take place at baseline, 10 weeks and 34 weeks post-randomisation. The primary outcome will be reduction in depression symptomatology 34 weeks post-randomisation as assessed using the Public Health Questionnaire-9 (PHQ-9). Secondary outcomes will include depressive symptomatology at 10 weeks post-randomisation and other clinical outcomes measured at 10-week and 34-week follow-up, along with a series of binarised outcomes to indicate clinically significant and reliable change. Evaluations of cost-effectiveness will be based on assessments of service use costs collected using the Adult Service Use Schedule and health utilities derived from the EQ-5D. DISCUSSION: This trial will add to the evidence base for the use of MBCT in depressed treatment non-responders. It will constitute the first trial to test MBCT following non-response to psychological therapy, with results providing a direct estimate of efficacy within the IAPT pathway. As such, its results will offer an important basis for decisions regarding the adoption of MBCT for non-responders within IAPT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05236959. Registered on 11 February 2022. ISRCTN 17755571. Registered on 2 February 2021.

Service use and costs in adolescents with pain and suicidality: a cross-sectional study.

Background: Persistent/recurrent pain for more than three months and suicidality (suicide and self-harm related thoughts and behaviours) are serious and co-occurring health problems in adolescence, underscoring the need for targeted support. However, little is known about service use and costs in adolescents with pain-suicidality comorbidity, compared to those with either problem alone. This study aimed to shed light on service use and costs in adolescents with pain and/or suicidality, and the role of individual and school characteristics. Methods: We analysed cross-sectional, pre-intervention data from a large cluster randomised controlled trial, collected between 2017 and 2019 on a representative sample of 8072 adolescents (55% female; aged 11-15 years; 76% white) in 84 schools in the UK. We explored service use settings, covering health, social, educational settings, and medication for mental health problems over three months. Data were analysed using descriptive statistics and two-part hurdle models to obtain odds ratios (ORs) and incident rate ratios (IRRs). Findings: 9% of adolescents reported comorbidity between pain and suicidality, 11% only suicidality, 13% only pain, and 66% neither pain nor suicidality. Approximately 55% of adolescents used services, especially general practitioner visits, outpatient appointments for injuries and contacts with a school nurse or pharmacist. Compared to adolescents with neither pain nor suicidality: (i) adolescents with pain (OR 3.79, 95% CI 2.63-5.48), suicidality (1.68, 1.12-2.51), and pain-suicidality comorbidity (2.35, 1.26-4.41) were more likely to use services and (ii) if services were used, they were more likely to have higher total costs (Pain: IRR 1.25, 95% CI 1.11-1.42; Suicidality: 1.27, 1.11-1.46; Comorbidity: 1.57, 1.34-1.85). Interpretation: In our study, adolescents with pain and suicidality reported increased contact with health, social, and educational services, which could provide an opportunity for suicide prevention. Given the diversity of identified settings, multi-sector suicide prevention strategies are paramount. Funding: Wellcome Trust [WT104908/Z/14/Z; WT107496/Z/15/Z]; Stiftung Oskar-Helene-Heim.

Effectiveness of universal school-based mindfulness training compared with normal school provision on teacher mental health and school climate: results of the MYRIAD cluster randomised controlled trial.

BACKGROUND: Education is broader than academic teaching. It includes teaching students social-emotional skills both directly and indirectly through a positive school climate. OBJECTIVE: To evaluate if a universal school-based mindfulness training (SBMT) enhances teacher mental health and school climate. METHODS: The My Resilience in Adolescence parallel group, cluster randomised controlled trial (registration: ISRCTN86619085; funding: Wellcome Trust (WT104908/Z/14/Z, WT107496/Z/15/Z)) recruited 85 schools (679 teachers) delivering social and emotional teaching across the UK. Schools (clusters) were randomised 1:1 to either continue this provision (teaching as usual (TAU)) or include universal SBMT. Data on teacher mental health and school climate were collected at prerandomisation, postpersonal mindfulness and SBMT teacher training, after delivering SBMT to students, and at 1-year follow-up. FINDING: Schools were recruited in academic years 2016/2017 and 2017/2018. Primary analysis (SBMT: 43 schools/362 teachers; TAU: 41 schools/310 teachers) showed that after delivering SBMT to students, SBMT versus TAU enhanced teachers' mental health (burnout) and school climate. Adjusted standardised mean differences (SBMT minus TAU) were: exhaustion (-0.22; 95% CI -0.38 to -0.05); personal accomplishment (-0.21; -0.41, -0.02); school leadership (0.24; 0.04, 0.44); and respectful climate (0.26; 0.06, 0.47). Effects on burnout were not significant at 1-year follow-up. Effects on school climate were maintained only for respectful climate. No SBMT-related serious adverse events were reported. CONCLUSIONS: SBMT supports short-term changes in teacher burnout and school climate. Further work is required to explore how best to sustain improvements. CLINICAL IMPLICATIONS: SBMT has limited effects on teachers' mental and school climate. Innovative approaches to support and preserve teachers' mental health and school climate are needed.

Effectiveness and cost-effectiveness of universal school-based mindfulness training compared with normal school provision in reducing risk of mental health problems and promoting well-being in adolescence: the MYRIAD cluster randomised controlled trial.

BACKGROUND: Systematic reviews suggest school-based mindfulness training (SBMT) shows promise in promoting student mental health. OBJECTIVE: The My Resilience in Adolescence (MYRIAD) Trial evaluated the effectiveness and cost-effectiveness of SBMT compared with teaching-as-usual (TAU). METHODS: MYRIAD was a parallel group, cluster-randomised controlled trial. Eighty-five eligible schools consented and were randomised 1:1 to TAU (43 schools, 4232 students) or SBMT (42 schools, 4144 students), stratified by school size, quality, type, deprivation and region. Schools and students (mean (SD); age range=12.2 (0.6); 11-14 years) were broadly UK population-representative. Forty-three schools (n=3678 pupils; 86.9%) delivering SBMT, and 41 schools (n=3572; 86.2%) delivering TAU, provided primary end-point data. SBMT comprised 10 lessons of psychoeducation and mindfulness practices. TAU comprised standard social-emotional teaching. Participant-level risk for depression, social-emotional-behavioural functioning and well-being at 1 year follow-up were the co-primary outcomes. Secondary and economic outcomes were included. FINDINGS: Analysis of 84 schools (n=8376 participants) found no evidence that SBMT was superior to TAU at 1 year. Standardised mean differences (intervention minus control) were: 0.005 (95% CI -0.05 to 0.06) for risk for depression; 0.02 (-0.02 to 0.07) for social-emotional-behavioural functioning; and 0.02 (-0.03 to 0.07) for well-being. SBMT had a high probability of cost-effectiveness (83%) at a willingness-to-pay threshold of £20 000 per quality-adjusted life year. No intervention-related adverse events were observed. CONCLUSIONS: Findings do not support the superiority of SBMT over TAU in promoting mental health in adolescence. CLINICAL IMPLICATIONS: There is need to ask what works, for whom and how, as well as considering key contextual and implementation factors. TRIAL REGISTRATION: Current controlled trials ISRCTN86619085. This research was funded by the Wellcome Trust (WT104908/Z/14/Z and WT107496/Z/15/Z).

The Reflective Fostering Programme-improving the wellbeing of children in care through a group intervention for foster carers: a randomised controlled trial.

BACKGROUND: The needs of children in care are a government priority, yet the evidence base for effective interventions to support the emotional wellbeing of children in care is lacking. Research suggests that supporting the carer-child relationship, by promoting the carer's reflective parenting, may be an effective approach to improving the wellbeing of these children. METHODS: The study comprises a definitive, superiority, two-armed, parallel, pragmatic, randomised controlled trial, with embedded process evaluation and economic evaluation, and an internal pilot, to evaluate the effectiveness, and cost-effectiveness, of the Reflective Fostering Programme. Randomisation is at the individual level using a 1:1 allocation ratio. The study is being conducted in local authority sites across England, and is targeted at foster carers (including kinship carers) looking after children aged 4 to 13. Consenting participants are randomly allocated to the Reflective Fostering Programme (intervention arm) in addition to usual support or usual support alone (control arm). The primary outcome is behavioural and emotional wellbeing of the child 12 months post-baseline, and secondary outcomes include the following: foster carer's level of stress, quality of life, reflective capacity, compassion fatigue and burnout, placement stability, the quality of the child-carer relationship, child's capacity for emotional regulation, and achievement of personalised goals set by the carer. DISCUSSION: A feasibility study has indicated effectiveness of the Programme in improving the child-carer relationship and emotional and behavioural wellbeing of children in care. This study will test the effectiveness and cost-effectiveness of implementing the Reflective Fostering Programme as an additional aid to the support already available to local authority foster carers. TRIAL REGISTRATION: ISRCTN 70832140 .

A video-feedback parenting intervention to prevent enduring behaviour problems in at-risk children aged 12-36 months: the Healthy Start, Happy Start RCT.

BACKGROUND: Behaviour problems emerge early in childhood and place children at risk for later psychopathology. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of a parenting intervention to prevent enduring behaviour problems in young children. DESIGN: A pragmatic, assessor-blinded, multisite, two-arm, parallel-group randomised controlled trial. SETTING: Health visiting services in six NHS trusts in England. PARTICIPANTS: A total of 300 at-risk children aged 12-36 months and their parents/caregivers. INTERVENTIONS: Families were allocated in a 1 : 1 ratio to six sessions of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) plus usual care or usual care alone. MAIN OUTCOME MEASURES: The primary outcome was the Preschool Parental Account of Children's Symptoms, which is a structured interview of behaviour symptoms. Secondary outcomes included caregiver-reported total problems on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The intervention effect was estimated using linear regression. Health and social care service use was recorded using the Child and Adolescent Service Use Schedule and cost-effectiveness was explored using the Preschool Parental Account of Children's Symptoms. RESULTS: In total, 300 families were randomised: 151 to VIPP-SD plus usual care and 149 to usual care alone. Follow-up data were available for 286 (VIPP-SD, n = 140; usual care, n = 146) participants and 282 (VIPP-SD, n = 140; usual care, n = 142) participants at 5 and 24 months, respectively. At the post-treatment (primary outcome) follow-up, a group difference of 2.03 on Preschool Parental Account of Children's Symptoms (95% confidence interval 0.06 to 4.01; p = 0.04) indicated a positive treatment effect on behaviour problems (Cohen's d = 0.20, 95% confidence interval 0.01 to 0.40). The effect was strongest for children's conduct [1.61, 95% confidence interval 0.44 to 2.78; p = 0.007 (d = 0.30, 95% confidence interval 0.08 to 0.51)] versus attention deficit hyperactivity disorder symptoms [0.29, 95% confidence interval -1.06 to 1.65; p = 0.67 (d = 0.05, 95% confidence interval -0.17 to 0.27)]. The Child Behaviour Checklist [3.24, 95% confidence interval -0.06 to 6.54; p = 0.05 (d = 0.15, 95% confidence interval 0.00 to 0.31)] and the Strengths and Difficulties Questionnaire [0.93, 95% confidence interval -0.03 to 1.9; p = 0.06 (d = 0.18, 95% confidence interval -0.01 to 0.36)] demonstrated similar positive treatment effects to those found for the Preschool Parental Account of Children's Symptoms. At 24 months, the group difference on the Preschool Parental Account of Children's Symptoms was 1.73 [95% confidence interval -0.24 to 3.71; p = 0.08 (d = 0.17, 95% confidence interval -0.02 to 0.37)]; the effect remained strongest for conduct [1.07, 95% confidence interval -0.06 to 2.20; p = 0.06 (d = 0.20, 95% confidence interval -0.01 to 0.42)] versus attention deficit hyperactivity disorder symptoms [0.62, 95% confidence interval -0.60 to 1.84; p = 0.32 (d = 0.10, 95% confidence interval -0.10 to 0.30)], with little evidence of an effect on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The primary economic analysis showed better outcomes in the VIPP-SD group at 24 months, but also higher costs than the usual-care group (adjusted mean difference £1450, 95% confidence interval £619 to £2281). No treatment- or trial-related adverse events were reported. The probability of VIPP-SD being cost-effective compared with usual care at the 24-month follow-up increased as willingness to pay for improvements on the Preschool Parental Account of Children's Symptoms increased, with VIPP-SD having the higher probability of being cost-effective at willingness-to-pay values above £800 per 1-point improvement on the Preschool Parental Account of Children's Symptoms. LIMITATIONS: The proportion of participants with graduate-level qualifications was higher than among the general public. CONCLUSIONS: VIPP-SD is effective in reducing behaviour problems in young children when delivered by health visiting teams. Most of the effect of VIPP-SD appears to be retained over 24 months. However, we can be less certain about its value for money. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58327365. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 29. See the NIHR Journals Library website for further project information.

Behaviour problems in young children are common and are linked to mental and physical health problems, and educational and social difficulties. An important factor that influences the development of behaviour problems is the quality of care that children receive from their caregivers. This study aimed to test if a six-session parenting programme [called Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD)] reduced behaviour problems in children aged 1 or 2 years who were showing early signs of behaviour problems (e.g. restlessness, impulsivity, tantrums and aggression). VIPP-SD supports caregivers in responding to their child's communication and behaviour. A total of 300 families participated. All families continued to access usual health-care services (e.g. health visitors and general practitioners), but half of the families were randomly allocated to also receive the VIPP-SD programme. We visited all families when the study started, and at 5 and 24 months to see if the children whose families received VIPP-SD showed fewer behaviour problems. We measured the children's behaviour by completing interviews and questionnaires with their caregivers. We also analysed whether or not VIPP-SD was good value for money compared with existing services. We did this by comparing the cost of all of the standard health and community services that families accessed during their time in the study, taking account of the impact that VIPP-SD had on children's behaviour. The children in the VIPP-SD group had lower levels of behaviour problems following the programme than children whose parents did not receive the programme. On average, VIPP-SD children scored 2 points lower on the main measure of behaviour; an example difference would be tantrums being rated as mild rather than severe. By the 2-year visit, the VIPP-SD children continued to show lower levels of behaviour problems. It is less clear whether or not VIPP-SD is good value for money, as this depends on how much money policy-makers are willing to invest for reductions in behaviour problems. Overall, there is strong evidence that the VIPP-SD programme is effective in reducing behaviour problems in the short term. Most of this benefit appears to be maintained for the following 2 years. However, we are less certain about the long-term effect and the VIPP-SD's value for money.

Update to the effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial.

BACKGROUND: MYRIAD (My Resilience in Adolescence) is a superiority, parallel group, cluster randomised controlled trial designed to examine the effectiveness and cost-effectiveness of a mindfulness training (MT) programme, compared with normal social and emotional learning (SEL) school provision to enhance mental health, social-emotional-behavioural functioning and well-being in adolescence. The original trial protocol was published in Trials (accessible at https://doi.org/10.1186/s13063-017-1917-4 ). This included recruitment in two cohorts, enabling the learning from the smaller first cohort to be incorporated in the second cohort. Here we describe final amendments to the study protocol and discuss their underlying rationale. METHODS: Four major changes were introduced into the study protocol: (1) there were changes in eligibility criteria, including a clearer operational definition to assess the degree of SEL implementation in schools, and also new criteria to avoid experimental contamination; (2) the number of schools and pupils that had to be recruited was increased based on what we learned in the first cohort; (3) some changes were made to the secondary outcome measures to improve their validity and ability to measure constructs of interest and to reduce the burden on school staff; and (4) the current Coronavirus Disease 2019 (SARS-CoV-2 or COVID-19) pandemic both influences and makes it difficult to interpret the 2-year follow-up primary endpoint results, so we changed our primary endpoint to 1-year follow-up. DISCUSSION: These changes to the study protocol were approved by the Trial Management Group, Trial Steering Committee and Data and Ethics Monitoring Committees and improved the enrolment of participants and quality of measures. Furthermore, the change in the primary endpoint will give a more reliable answer to our primary question because it was collected prior to the COVID-19 pandemic in both cohort 1 and cohort 2. Nevertheless, the longer 2-year follow-up data will still be acquired, although this time-point will be now framed as a second major investigation to answer some new important questions presented by the combination of the pandemic and our study design. TRIAL REGISTRATION: International Standard Randomised Controlled Trials ISRCTN86619085 . Registered on 3 June 2016.

A Brief Home-Based Parenting Intervention to Reduce Behavior Problems in Young Children: A Pragmatic Randomized Clinical Trial.

Importance: Behavior problems are one of the most common mental health disorders in childhood and can undermine children's health, education, and employment outcomes into adulthood. There are few effective interventions for early childhood. Objective: To test the clinical effectiveness of a brief parenting intervention, the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD), in reducing behavior problems in children aged 12 to 36 months. Design, Setting, and Participants: The Healthy Start, Happy Start study was a 2-group, parallel-group, researcher-blind, multisite randomized clinical trial conducted via health visiting services in 6 National Health Service trusts in England. Baseline and 5-month follow-up data were collected between July 30, 2015, and April 27, 2018. Of 818 eligible families, 227 declined to participate, and 300 were randomized into the trial. Target participants were caregivers of children who scored in the top 20% for behavior problems on the Strengths and Difficulties Questionnaire. Participants were randomly allocated on a 1:1 basis to receive either VIPP-SD (n = 151) or usual care (n = 149), stratified by site and number of participating caregivers. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from September 5, 2019, to January 17, 2020. Interventions: All families continued to access usual care. Families allocated to VIPP-SD were offered 6 home-based video-feedback sessions of 1 to 2 hours' duration every 2 weeks. Main Outcomes and Measures: The primary outcome was the score on an early childhood version of the Preschool Parental Account of Children's Symptoms, a semistructured interview of behavior symptoms, at 5 months after randomization. Secondary outcomes included caregiver-reported behavior problems on the Child Behavior Checklist and the Strengths and Difficulties Questionnaire. Results: Among 300 participating children (163 boys [54%]; mean [SD] age, 23.0 [6.7] months), primary outcome data were available for 140 of 151 VIPP-SD participants (93%) and 146 of 149 usual care participants (98%). There was a mean difference in the total Preschool Parental Account of Children's Symptoms score of 2.03 (95% CI, 0.06-4.01; P = .04; Cohen d = 0.20 [95% CI, 0.01-0.40]) between trial groups, with fewer behavior problems in the VIPP-SD group, particularly conduct symptoms (mean difference, 1.61 [95% CI, 0.44-2.78]; P = .007; d = 0.30 [95% CI, 0.08-0.51]). Other child behavior outcomes showed similar evidence favoring VIPP-SD. No treatment or trial-related adverse events were reported. Conclusions and Relevance: This study found that VIPP-SD was effective in reducing symptoms of early behavior problems in young children when delivered in a routine health service context. Trial Registration: isrctn.org Identifier: ISRCTN58327365.

M.I.C.E-Mental Health Intervention for Children with Epilepsy: a randomised controlled, multi-centre clinical trial evaluating the clinical and cost-effectiveness of MATCH-ADTC in addition to usual care compared to usual care alone for children and young people with common mental health disorders and epilepsy-study protocol.

BACKGROUND: Mental health disorders in the context of long-term conditions in children and young people are currently overlooked and undertreated. Evidence-based psychological treatments for common childhood mental health disorders (anxiety, depression and disruptive behaviour disorders) have not been systematically evaluated in young people with epilepsy despite their high prevalence in this population. The aim of this multi-site randomised controlled trial is to determine the clinical and cost-effectiveness of adding a modular psychological intervention to usual care for the mental health disorders in comparison to assessment-enhanced usual care alone. METHODS: In total, 334 participants aged 3-18 years attending epilepsy services will be screened for mental health disorders with the Strengths and Difficulties Questionnaire (SDQ) and the diagnostic Development and Wellbeing Assessment (DAWBA). Those identified as having a mental health disorder and consenting to the trial will be randomised to either receive up to 22 sessions of the modular psychological intervention (MATCH-ADTC) delivered over the telephone over 6 months by non-mental health professionals in addition to usual care or to assessment-enhanced usual care alone. Outcomes will be measured at baseline, 6 months and 12 months post-randomisation. It is hypothesised that MATCH-ADTC plus usual care will be superior to assessment-enhanced usual care in improving emotional and behavioural symptoms. The primary outcome is the SDQ reported by parents at 6 months. Secondary outcomes include parent-reported mental health measures such as the Revised Children's Anxiety and Depression Scale, quality of life measures such as the Paediatric Quality of Life Inventory and physical health measures such as the Hague Seizure Severity Scale. Outcome assessors will be blinded to group assignment. Qualitative process evaluations and a health economic evaluation will also be completed. DISCUSSION: This trial aims to determine whether a systematic and integrated approach to the identification and treatment of mental health disorders in children and young people with epilepsy is clinically and cost-effective. The findings will contribute to policies and practice with regard to addressing mental health needs in children and young people with other long-term conditions. TRIAL REGISTRATION: ISRCTN ISRCTN57823197 . Registered on 25 February 2019.

Multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): 5-year follow-up of a pragmatic, randomised, controlled, superiority trial.

BACKGROUND: Multisystemic therapy is a manualised treatment programme for young people aged 11-17 years who exhibit antisocial behaviour. To our knowledge, the Systemic Therapy for At Risk Teens (START) trial is the first large-scale randomised controlled trial of multisystemic therapy in the UK. Previous findings reported to 18 months after baseline (START-I study) did not indicate superiority of multisystemic therapy compared with management as usual. Here, we report outcomes of the trial to 60 months (START-II study). METHODS: In this pragmatic, randomised, controlled, superiority trial, young people (aged 11-17 years) with moderate-to-severe antisocial behaviour were recruited from social services, youth offending teams, schools, child and adolescent mental health services, and voluntary services across England, UK. Participants were eligible if they had at least three severity criteria indicating past difficulties across several settings and one of five general inclusion criteria for antisocial behaviour. Eligible families were randomly assigned (1:1), using stochastic minimisation and stratifying for treatment centre, sex, age at enrolment, and age at onset of antisocial behaviour, to management as usual or 3-5 months of multisystemic therapy followed by management as usual. Research assistants and investigators were masked to treatment allocation; the participants could not be masked. For this extension study, the primary outcome was the proportion of participants with offences with convictions in each group at 60 months after randomisation. This study is registered with ISRCTN, ISRCTN77132214, and is closed to accrual. FINDINGS: Between Feb 4, 2010, and Sept 1, 2012, 1076 young people and families were assessed for eligibility and 684 were randomly assigned to management as usual (n=342) or multisystemic therapy (n=342). By 60 months' of follow-up, 188 (55%) of 342 people in the multisystemic therapy group had at least one offence with a criminal conviction, compared with 180 (53%) of 341 in the management-as-usual group (odds ratio 1·13, 95% CI 0·82-1·56; p=0·44). INTERPRETATION: The results of the 5-year follow-up show no evidence of longer-term superiority for multisystemic therapy compared with management as usual. FUNDING: National Institute for Health Research Health Services and Delivery Research programme.

Can General Practitioners manage mental disorders in primary care? A partially randomised, pragmatic, cluster trial.

BACKGROUND: For a decade, experts have suggested integrating mental health care into primary care to help bridge mental health Treatment Gap. General Practitioners (GPs) are the first port-of-call for many patients with mental ill-health. In Indonesia, the WHO mhGAP is being systematically introduced to its network of 10,000 primary care clinics as an add-on mental health training for pairs of GPs and Nurses, since the end of 2015. In one of 34 provinces, there exists an integrated care model: the co-location of clinical psychologists in primary care clinics. This trial evaluates patient outcomes among those provided mental health care by GPs with those treated by clinical psychologists in primary care. METHODS: In this partially-randomised, pragmatic, two-arm cluster non-inferiority trial, 14 primary care clinics were assigned to receive the WHO mhGAP training and 14 clinics with the co-location framework were assigned to the Specialist arm. Participants (patients) were blinded to the existence of the other pathway, and outcome assessors were blinded to group assignment. All adult primary care patients who screened positive for psychiatric morbidity were eligible. GPs offered psychosocial and/or pharmacological interventions and Clinical Psychologists offered psychosocial interventions. The primary outcome was health and social functioning as measured by the HoNOS and secondary outcomes include disability measured by WHODAS 2.0, health-related quality of life measured by EQ-5D-3L, and resource use and costs evaluated from a health services perspective, at six months. RESULTS: 153 patients completed the outcome assessment following GP care alongside 141 patients following Clinical Psychologists care. Outcomes of GP care were proven to be statistically not inferior to Clinical Psychologists in reducing symptoms of social and physical impairment, reducing disability, and improving health-related quality of life at six months. Economic analyses indicate lower costs and better outcomes in the Specialist arm and suggest a 50% probability of WHO mhGAP framework being cost-effective at the Indonesian willingness to pay threshold per QALY. CONCLUSION: General Practitioners supported by nurses in primary care clinics could effectively manage mild to moderate mental health issues commonly found among primary care patients. They provide non-stigmatising mental health care within community context, helping to reduce the mental health Treatment Gap. TRIAL REGISTRATION: ClinicalTrials.gov NCT02700490.

The effectiveness and cost-effectiveness of the Incredible Years® Teacher Classroom Management programme in primary school children: results of the STARS cluster randomised controlled trial.

BACKGROUND: We evaluated the effectiveness and cost-effectiveness of the Incredible Years® Teacher Classroom Management (TCM) programme as a universal intervention, given schools' important influence on child mental health. METHODS: A two-arm, pragmatic, parallel group, superiority, cluster randomised controlled trial recruited three cohorts of schools (clusters) between 2012 and 2014, randomising them to TCM (intervention) or Teaching As Usual (TAU-control). TCM was delivered to teachers in six whole-day sessions, spread over 6 months. Schools and teachers were not masked to allocation. The primary outcome was teacher-reported Strengths and Difficulties Questionnaire (SDQ) Total Difficulties score. Random effects linear regression and marginal logistic regression models using Generalised Estimating Equations were used to analyse the outcomes. TRIAL REGISTRATION: ISRCTN84130388. RESULTS: Eighty schools (2075 children) were enrolled; 40 (1037 children) to TCM and 40 (1038 children) to TAU. Outcome data were collected at 9, 18, and 30-months for 96, 89, and 85% of children, respectively. The intervention reduced the SDQ-Total Difficulties score at 9 months (mean (s.d.):5.5 (5.4) in TCM v. 6.2 (6.2) in TAU; adjusted mean difference = -1.0; 95% CI-1.9 to -0.1; p = 0.03) but this did not persist at 18 or 30 months. Cost-effectiveness analysis suggested that TCM may be cost-effective compared with TAU at 30-months, but this result was associated with uncertainty so no firm conclusions can be drawn. A priori subgroup analyses suggested TCM is more effective for children with poor mental health. CONCLUSIONS: TCM provided a small, short-term improvement to children's mental health particularly for children who are already struggling.

Lamotrigine for people with borderline personality disorder: a RCT.

BACKGROUND: No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD. OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD. DESIGN: A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms. SETTING: Secondary care NHS mental health services in six centres in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant. INTERVENTIONS: Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day. MAIN OUTCOME MEASURES: Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes. RESULTS: Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0; p = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. LIMITATIONS: Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health. CONCLUSIONS: The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources. FUTURE WORK: Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90916365. FUNDING: Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in Health Technology Assessment; Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morriss' salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands.

The Clinical Effectiveness and Cost-Effectiveness of Lamotrigine in Borderline Personality Disorder: A Randomized Placebo-Controlled Trial.

OBJECTIVE: The authors examined whether lamotrigine is a clinically effective and cost-effective treatment for people with borderline personality disorder. METHOD: This was a multicenter, double-blind, placebo-controlled randomized trial. Between July 2013 and November 2016, the authors recruited 276 people age 18 or over who met diagnostic criteria for borderline personality disorder. Individuals with coexisting bipolar affective disorder or psychosis, those already taking a mood stabilizer, and women at risk of pregnancy were excluded. A web-based randomization service was used to allocate participants randomly in a 1:1 ratio to receive either an inert placebo or up to 400 mg/day of lamotrigine. The primary outcome measure was score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. Secondary outcome measures included depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment, and adverse events. RESULTS: A total of 195 (70.6%) participants were followed up at 52 weeks, at which point 49 (36%) of those in the lamotrigine group and 58 (42%) of those in the placebo group were taking study medication. The mean ZAN-BPD score was 11.3 (SD=6.6) among those in the lamotrigine group and 11.5 (SD=7.7) among those in the placebo group (adjusted difference in means=0.1, 95% CI=-1.8, 2.0). There was no evidence of any differences in secondary outcomes. Costs of direct care were similar in the two groups. CONCLUSIONS: The results suggest that treating people with borderline personality disorder with lamotrigine is not a clinically effective or cost-effective use of resources.

Multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): a pragmatic, randomised controlled, superiority trial.

BACKGROUND: Adolescent antisocial behaviour is a major health and social problem. Studies in the USA have shown that multisystemic therapy reduces such behaviour and the number of criminal offences committed by this group. However, findings outside the USA are equivocal. We aimed to assess the effectiveness and cost-effectiveness of multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour. METHODS: We did an 18 month, multisite, pragmatic, randomised controlled, superiority trial in England. Eligible participants aged 11-17 years with moderate-to-severe antisocial behaviour had at least three severity criteria indicating past difficulties across several settings and one of five general inclusion criteria for antisocial behaviour. We randomly assigned families (1:1) using stochastic minimisation, stratifying for treatment centre, sex, age at enrolment to study, and age at onset of antisocial behaviour, to receive either management as usual or 3-5 months of multisystemic therapy followed by management as usual. Research assistants and investigators were masked to treatment allocation; the participants could not be masked. The primary outcome was out-of-home placement at 18 months. The primary analysis included all randomised participants for whom data were available. This trial is registered, number ISRCTN77132214. Follow-up of the trial is still ongoing. FINDINGS: Between Feb 4, 2010, and Sept 1, 2012, 1076 families were referred to nine multi-agency panels, 684 of whom were assigned to management as usual (n=342) or multisystemic therapy followed by management as usual (n=342). At 18 months, the proportion of participants in out-of-home placement was not significantly different between the groups (13% [43/340] in the multisystemic therapy group vs 11% [36/335] in the management-as-usual group; odds ratio 1·25, 95% CI 0·77-2·05; p=0·37). INTERPRETATION: The findings do not support that multisystemic therapy should be used over management as usual as the intervention of choice for adolescents with moderate-to-severe antisocial behaviour. FUNDING: Department for Children, Schools and Families, Department of Health.

Cost and Outcome of BehaviouRal Activation (COBRA): a randomised controlled trial of behavioural activation versus cognitive-behavioural therapy for depression.

BACKGROUND: Depression is a common, debilitating and costly disorder. The best-evidenced psychological therapy - cognitive-behavioural therapy (CBT) - is complex and costly. A simpler therapy, behavioural activation (BA), may be an effective alternative. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of BA compared with CBT for depressed adults at 12 and 18 months' follow-up, and to investigate the processes of treatments. DESIGN: Randomised controlled, non-inferiority trial stratified by depression severity, antidepressant use and recruitment site, with embedded process evaluation; and randomisation by remote computer-generated allocation. SETTING: Three community mental health services in England. PARTICIPANTS: Adults aged ≥ 18 years with major depressive disorder (MDD) recruited from primary care and psychological therapy services. INTERVENTIONS: BA delivered by NHS junior mental health workers (MHWs); CBT by NHS psychological therapists. OUTCOMES: Primary: depression severity (as measured via the Patient Health Questionnaire-9; PHQ-9) at 12 months. Secondary: MDD status; number of depression-free days; anxiety (as measured via the Generalised Anxiety Disorder-7); health-related quality of life (as measured via the Short Form questionnaire-36 items) at 6, 12 and 18 months; and PHQ-9 at 6 and 18 months, all collected by assessors blinded to treatment allocation. Non-inferiority margin was 1.9 PHQ-9 points. We undertook intention-to-treat (ITT) and per protocol (PP) analyses. We explored cost-effectiveness by collecting direct treatment and other health- and social-care costs and calculating quality-adjusted life-years (QALYs) using the EuroQol-5 Dimensions, three-level version, at 18 months. RESULTS: We recruited 440 participants (BA, n = 221; CBT, n = 219); 175 (79%) BA and 189 (86%) CBT participants provided ITT data and 135 (61%) BA and 151 (69%) CBT participants provided PP data. At 12 months we found that BA was non-inferior to CBT {ITT: CBT 8.4 PHQ-9 points [standard deviation (SD) 7.5 PHQ-9 points], BA 8.4 PHQ-9 points (SD 7.0 PHQ-9 points), mean difference 0.1 PHQ-9 points, 95% confidence interval (CI) -1.3 to 1.5 PHQ-9 points, p = 0.89; PP: CBT 7.9 PHQ-9 points (SD 7.3 PHQ-9 points), BA 7.8 PHQ-9 points (SD 6.5 PHQ-9 points), mean difference 0.0 PHQ-9 points, 95% CI -1.5 to 1.6 PHQ-9 points, p = 0.99}. We found no differences in secondary outcomes. We found a significant difference in mean intervention costs (BA, £975; CBT, £1235; p < 0.001), but no differences in non-intervention (hospital, community health, social care and medication costs) or total (non-intervention plus intervention) costs. Costs were lower and QALY outcomes better in the BA group, generating an incremental cost-effectiveness ratio of -£6865. The probability of BA being cost-effective compared with CBT was almost 80% at the National Institute for Health and Care Excellence's preferred willingness-to-pay threshold of £20,000-30,000 per QALY. There were no trial-related adverse events. LIMITATIONS: In this pragmatic trial many depressed participants in both groups were also taking antidepressant medication, although most had been doing so for a considerable time before entering the trial. Around one-third of participants chose not to complete a PP dose of treatment, a finding common in both psychotherapy trials and routine practice. CONCLUSIONS: We found that BA is as effective as CBT, more cost-effective and can be delivered by MHWs with no professional training in psychological therapies. FUTURE WORK: Settings and countries with a paucity of professionally qualified psychological therapists, might choose to investigate the delivery of effective psychological therapy for depression without the need to develop an extensive and costly professional infrastructure. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27473954. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 46. See the NIHR Journals Library website for further project information.