PRODIGY: Prevention and treatment of long-term social disability amongst young people with emerging severe mental illness: A randomised controlled trial of clinical and cost-effectiveness of Social Recovery Therapy

Abstract

Background

Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological intervention.

Aims

We aimed to test the hypothesis that adding Social Recovery Therapy (SRT) to Enhanced Standard Care (ESC) would improve social recovery compared to ESC alone.

Methods

A pragmatic, assessor-blind, randomised controlled trial (PRODIGY: ISRCTN47998710, 29/11/2012) was conducted in three UK centres. Participants (N=270) were aged 16-25 years, with persistent social disability defined as under 30 weekly hours of structured activity and social impairment for six months plus, and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over nine months. The primary outcome was structured activity 15-months post-randomisation.

Results

One-hundred-and-thirty-two participants were randomised to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15-months increased by 11.1 hours for SRT plus ESC (M=22.4, SD=21.4) and 16.6 hours for ESC alone (M=27.7, (SD=26.5). There was no significant difference; treatment effect= -4.44, 95% confidence intervals -10.19—1.31, p=0.13. Missingness was consistently greater in ESC alone.

Conclusions

We found no evidence for the superiority of SRT as adjunctive to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing adjunctive specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.

Relevance statement

This important definitive trial focusses on an important and neglected group of young people with severe problems, who have not experienced an episode of psychosis, that are socially withdrawn. The results of the trial are surprising in showing no specific benefit for the candidate psychological therapy (Social Recovery Therapy). Instead, both the intervention and control group show very large gains in multiple markers of symptomatic and functional recovery, despite having severe and complex problems at outset. These results therefore show the tremendous potential for recovery in a group, often considered very difficult to engage and intractable, if comprehensive assessment and treatment is provided.

Introduction

Three quarters of socially disabling long-term mental health problems begin in adolescence(7). Social disability is observable before the onset of mental health problems, and when ongoing, transition to long-term problems of diagnostic severity is more likely(2,8). Social disability can be defined as low time spent in structured activity. Young people without mental health problems spend 64 weekly hours on average in structured activity, with under 30 hours representing serious social disability and under 15 severe social disability(9). Structured activities include paid and voluntary employment, education, caring, sports, and leisure(9). Young people at the greatest risk of long-term social disability present with emerging social withdrawal, emotional and behavioural problems, subthreshold psychosis, and risky behaviours, e.g. alcohol and drug use(7). This group is extremely vulnerable and their problems, if untreated, have severe, potentially lifelong personal and economic costs(7,10). This group is neglected in research and clinical care, with under 25% of young people with a diagnosable mental health problem gaining access to specialist mental health services(11). The significant social withdrawal makes engagement very challenging(2,5) and standard interventions may be inaccessible and ineffective. Recent reviews demonstrate Cognitive Behavioural Therapy (CBT) has only small or short-term effects on social outcomes for people at risk of psychosis or with schizophrenia(12,13). Youth community services, for example serving young people Not in Employment, Education or Training (NEET), often provide excellent vocational support but lack the requisite mental health specialism for this complex group(14). Vocational interventions delivered in mental health services, such as Individual Placement and Support, are effective in increasing paid employment for people with serious mental health problems, but do not target broader clinical and social outcomes(15). Early Intervention in Psychosis (EIP) services assertively engage people in specialist mental health and socio-occupational support in the context of complexity, but are only accessible with a confirmed or imminent first episode of psychosis, thus excluding people with non-psychotic yet severe and complex mental health problems. Furthermore, most people accessing EIP still experience persistent social disability one year later(16), and non-psychosis specific youth mental health services, where these exist, only effect reliable change for a minority(4).

We developed Social Recovery Therapy (SRT), a specialist psychosocial intervention combining CBT, assertive outreach, and multisystemic principles to treat social disability in the context of severe and complex mental health problems(17). The clinical and cost-effectiveness of SRT was demonstrated in psychosis(18,19). The SUPEREDEN3 trial(19) showed that adding SRT to EIP produced large and significant improvements in structured activity, psychotic and mood symptoms. We hypothesised that providing SRT to a younger group with emerging severe problems would create early gains in social and clinical recovery, interrupting potentially lifelong trajectories of disability. We conducted the PRODIGY trial to test the benefit of adding SRT to optimised standard care for young people with severe and complex mental health problems, who have not experienced an episode of psychosis. We conducted a qualitative process evaluation alongside the trial(20,21). Here we present the trial outcomes. We aimed to test the primary hypothesis that SRT as adjunctive to enhanced standard care (ESC) would be superior to ESC alone in improving weekly hours in structured activity at 15-months post-randomisation(1). Secondary hypotheses were that the addition of SRT would lead to greater improvements in psychotic, mood and general symptoms at 9- and 15-months and that improvements would persist until 24-months post-randomisation(1).

Methods

Study design

This trial was a pragmatic, multi-centre, single (assessor) blind, Randomised Controlled Trial comparing the clinical and cost-effectiveness of Social Recovery Therapy (SRT) and Enhanced Standard Care (ESC) to ESC alone. The intervention period lasted 9-months post-randomisation. Outcomes were assessed at 9- and 15-months post-randomisation, with limited assessment of longer-term outcomes at 24-months post-randomisation.

Participants

The target sample size was 270 participants, 135 in each arm(1). This target was calculated using a minimal clinically important effect size of 0.4 standard deviations in weekly structured activity hours, with 90% statistical power, two-sided 5% significance level, and allowing 20% attrition. Inclusion criteria were: aged 16-25 years; persistent social disability; severe and complex mental health problems. Persistent social disability was operationalised as under 30 weekly hours of structured activity, with history of social impairment for at least six months. The presence of severe and complex mental health problems was operationalised as meeting At Risk Mental States (ARMS) for psychosis criteria and/or scoring 50 or below on the Global Assessment of Functioning Scale (indicating at least serious symptoms and/or serious impairment in social, occupational or school functioning) with persistence of at least moderate symptoms for six months plus. Exclusion criteria were: active psychotic symptoms or history of psychosis measured using CAARMS criteria; severe learning disability; non-English speaking, or disease or physical problems likely to undermine participation. Participants were recruited from primary and secondary youth and adult NHS mental health services, third sector, youth, and education organisations.

Randomisation and masking

Following baseline assessment, participants were randomly allocated 1:1 to receive SRT plus ESC or ESC alone. Remote randomisation was performed by Norwich Clinical Trials Unit (NCTU) using predetermined lists with randomly distributed block sizes of 4 or 6. Randomisation was stratified by age (16-19/20-25 years); site (Sussex/East Anglia/Manchester); social disability severity (low functioning= 16-30 weekly hours of structured activity/very low functioning= 0-15 weekly hours) and whether ARMS criteria were met. The allocation sequence was hidden from all system users. A remote web-based system notified the allocation to NCTU and nominated trial staff.

Research Assistants collecting baseline and follow-up data were masked to intervention allocation. Masking was maintained by restricted access to the data management system and in-office precautions. Thirty-one un-maskings occurred during the trial, in which the assessor became aware of whether a participant had or had not received SRT in addition to ESC. All un-maskings were successfully managed by re-allocating outcome data collection to another masked assessor.

Procedures

Ethical approval was provided by the East of England Research Ethics Committee (12/EE/0311) and the Preston Research Ethics Committee-North West (15/NW/0590). Potentially eligible participants were approached by their usual care provider, who permissibly shared contact details with the research team. Potential participants were provided with written and verbal information describing trial involvement, and were invited to provide written informed consent and complete a screening assessment. Eligibility was confirmed through trial management group review. Eligible participants completed a baseline assessment and were randomised.

All participants received Enhanced Standard Care (ESC). ESC involved services already received or offered throughout the trial, including psychological therapies where applicable. We anticipated that standard care might be limited and inaccessible. We enhanced standard care by offering a comprehensive assessment report, detailing current mental health and social functioning, to all participants and providers at trial entry and follow-up assessments. Providers were additionally given a comprehensive best practice guide, detailing local services and organisations to which participants could be referred. Providers were encouraged to offer optimal clinical evidence-based services according to NICE guidelines. All three participating research sites were centres of excellence for youth mental health and psychosis.

Participants randomised to Social Recovery Therapy (SRT) plus ESC additionally received up to nine months of individual SRT sessions. SRT (www.socialrecoverytherapy.co.uk) incorporates assertive outreach, multisystemic and CBT techniques. Compared to traditional CBT, SRT focuses on assessment and formulation of barriers to social recovery, with a particular focus on using behavioural work and engaging with structured activity providers and others in the surrounding system to maintain social recovery. SRT was delivered according to the therapy manual(17). First, efforts were made to initiate engagement and develop a positive therapeutic relationship, with assessment of goals and barriers used to derive a social recovery formulation. Sessions are intended to be weekly at outset, reducing to fortnightly or monthly toward the end of the intervention period. Behavioural assessment during in vivo activities in the community informed the assessment and formulation. Following this, therapy focused on increasing time spent in structured activities linked to personal goals. Cognitive techniques promoted hopefulness and addressed negative beliefs about the self and others. Multilayered behavioural experiments were used to manage symptoms whilst engaging in structured activity; examples are provided in the therapy manual(17). SRT appears to improve structured activity through augmenting positive self-beliefs(22). SRT therapists were Clinical Psychologists, Occupational Therapists, or Mental Health Nurses with CBT accreditation. All therapists received training in SRT and regular expert individual and peer supervision. Three raters measured SRT adherence with our developed checklist(23) using session audiotapes and therapist notes. Inter-rater, reliability was excellent; Krippendorff’s alpha= 0.9, 95% CIs 0.87—0.98. A full SRT dose was defined as six plus sessions, with a social recovery assessment and formulation, and two plus pieces of behavioural work in the community with the therapist. Adherence data showed that 64% of sessions included behavioural work, 36% of which included a behavioural experiment. Of the face-to-face sessions, 53% were delivered in the patient’s home, 24% in the community (e.g. meeting in a city centre), 10% in an educational setting (e.g. meeting at college), and 13% in a clinic setting. Therapist competence was rated using session audiotapes. Competence was defined as a total score of 36 plus on the Cognitive Therapy Scale-Revised (CTS-R)(24). The CTS-R measures the therapist’s general competence in delivering cognitive therapy, i.e. using therapeutic skills and techniques, such as collaboration and feedback, to support cognitive change.

Outcomes

Participants were assessed at baseline, 9- and 15-months post-randomisation, with limited assessment of maintenance at 24-months. Research assistants used flexible, assertive engagement to facilitate involvement, conducting assessments mainly in participants’ homes. High inter-rater reliability for assessor-rated measures was ensured through regular supervision and training.

The primary outcome was weekly hours spent in structured activity(9). Using a structured interview derived from the Office of National Statistics Time Use Survey(25), time spent over the past month in structured activity was captured. Past month activity was divided to reflect average weekly hours in constructive economic (paid and voluntary employment, childcare, housework, and chores) and structured activity (constructive economic activity plus sports and leisure). The primary endpoint was 15-months post-randomisation.

Levels of attenuated psychotic symptoms were measured using the Comprehensive Assessment of At Risk Mental States (CAARMS). Derived outcomes included transition to psychosis and CAARMS symptom severity and symptom distress scores(26). Negative symptoms were assessed using the Schedule for Assessment of Negative Symptoms (SANS). General psychopathology was measured as change in mood, anxiety, somatoform and eating disorders using the Structured Clinical Interview for DSM-IV, and additionally with the self-report Beck Depression Inventory II (BDI-II), Social Anxiety Interaction Scale (SIAS), and assessor-rated Global Assessment of Functioning (GAF), Global Assessment of Symptoms (GAS), and Social and Occupational Functioning Scales (SOFAS). Putative mediators were assessed using Acceptance and Avoidance Questionnaire II (AAQ-II), Meaning in Life Questionnaire (MLQ), Trait Hope Scale (THS), Brief Core Schema Scales (BCSS), and Schizotypal Symptoms Inventory (SSI). Putative moderators were verbal memory, captured using the Logical Memory I subtest of the Wechsler Memory Scale, Third Edition (LMS), and verbal fluency, captured using the Controlled Oral Word Association Test (COWAT). Other outcomes were the Beck Hopelessness Scale (BHS), Alcohol Use Disorders Identification Test (AUDIT) and Drug Use Disorders Identification Test (DUDIT). Health economic outcomes were NHS and personal social service use, captured using the Health Service Resource Use Questionnaire, and health-related quality of life captured using the EuroQol-5D. Adverse events were recorded throughout the trial and reported to trial oversight committees.

Statistical analysis

Primary and secondary hypotheses were pre-registered (ISRCTN47998710 29/11/2012) and published in the protocol(1). A detailed statistical analysis plan was agreed between chief investigators, trial manager, trial statistician and health economist on 04/07/2018, prior to analysis. The primary analysis was intention to treat (ITT) comparing SRT plus ESC to ESC alone on weekly structured activity hours at 15-months post-randomisation. A per protocol analysis was additionally conducted, involving participants receiving full dose SRT. All analyses were conducted by the trial statistician and health economist. All hypothesis testing was conducted using a two-sided significance level of 5%, with corresponding 95% confidence intervals.

We anticipated the primary outcome might have positive skew and require a logarithmic transformation. Assuming Normal (or transformed to Normal) distribution, a general linear model was constructed for primary and then secondary analyses. For the primary outcome analyses, baseline logical memory and verbal fluency were included as prognostic variables, alongside stratification variables (site as a random factor) and allocation. Secondary outcomes were analysed using an analogous approach: a linear model with appropriate link for the outcome (e.g. logistic regression for binary outcomes), and including stratification variables, pre-defined prognostic variables and allocation. Available baseline values of the outcome were included. Planned moderation analysis considered the impact on the intervention effect of baseline social disability (low or very low functioning), ARMS status, logical memory, and verbal fluency. One addition was made to the statistical analysis plan after publication of the registered trial protocol; adding models which excluded time spent in childcare, as an imbalance towards females that considerably inflates structured activity. Both model types are presented here. Analyses were conducted using SAS (version 9.4).

Health economic outcomes were analysed using a within-trial cost-utility ITT approach, where costs (at 2017/2018 levels) and benefits were estimated over 24-months, with a 3.5% discount in the second year. SRT costs included therapy training, supervision, and delivery. ESC costs were derived from reported service attendances. Total quality-adjusted life-year (QALY) scores were estimated using EQ-5D-3L data. Regression was used to estimate (separately) the mean incremental cost and mean QALY gain. The incremental cost-effectiveness ratio (ICER) (mean incremental cost/mean QALY gain) was estimated, with value for money corresponding to the cost-effectiveness threshold of £20,000 per QALY. The level of uncertainty, according to the cost-effectiveness acceptability curve, was assessed at the same cost-effectiveness threshold value. Multiple imputation was used in the basecase analysis.

Results

One-hundred participants were recruited in an internal pilot, from 01/01/2013 until 01/02/2014 (n=50 East Anglia, n=50 Manchester). The remaining 170 participants (n=57 Sussex, n=59 East Anglia, n=54 Manchester) were recruited in an extension phase between 01/09/2015 and 31/05/2017. In total, 270 participants were randomised to receive Social Recovery Therapy (SRT) plus Enhanced Standard Care (ESC) (n=138) or ESC alone (n=132). Baseline characteristics were similar across groups (table 1). The ESC alone group was evenly balanced between sexes, however, the SRT plus ESC group over-represented males. Baseline data (table 2) reflect severe social disability and mental health symptoms. Most participants met diagnostic criteria for major depression and almost half for current social phobia.

Table 1. Baseline characteristics of the study population.

Characteristic		SRT + ESC N = 138	ESC alone N = 132
Age Group	16 to 19	79 (57%)	75 (57%)
	20 to 25	59 (43%)	57 (43%)
Age	Mean (SD)	20.1 (2.5)	20.0 (2.7)
	Missing	6	5
Gender	Female	54 (39%)	66 (50%)
	Male	84 (61%)	66 (50%)
Ethnicity	White	127 (92%)	114 (86%)
	Non-white	11 (8.0%)	18 (14%)
Marital Status	Partner	18 (13%)	17 (13%)
	Separated	2 (1.5%)	0
	Single	118 (86%)	115 (87%)
Employment Status	Paid work	5 (3.6%)	6 (4.6%)
	Voluntary work	3 (2.2%)	4 (3.0%)
	Student	34 (25%)	31 (24%)
	Unemployed	95 (69%)	91 (69%)
	Missing	1	0
Sexual Orientation	Heterosexual	98 (74%)	107 (82%)
	Homosexual	6 (4.5%)	6 (4.6%)
	Bisexual	16 (12.1%)	13 (9.9%)
	Unsure	6 (4.5%)	1 (0.8%)
	Other	6 (4.5%)	4 (3.1%)
	Missing	6	1
Accommodation	Accommodation with support	8 (5.9%)	4 (3.0%)
	Homeless/Temporary Accommodation	5 (3.7%)	7 (5.3%)
	Mobile Accommodation	0	1 (0.8%)
	Owner Occupied	48 (36%)	41 (31%)
	Rented (Local Authority/Housing Association)	45 (33%)	55 (42%)
	Rented (Private)	29 (22%)	24 (18%)
	Missing	3	0
Social	Low Functioning	40 (29%)	40 (30%)
Disability	Very Low Functioning	98 (71%)	92 (70%)
ARMS status	At Risk	69 (50%)	64 (49%)
	Not at Risk	69 (50%)	68 (52%)

Data are n (%) or mean (SD), unless otherwise specified. ARMS= At Risk Mental States for psychosis. Group differences were not statistically tested at baseline.

Table 2. Descriptive outcome data.

	Baseline		9 months		15 months		24 months
Outcome	Social Recovery Therapy plus Enhanced Standard Care	Enhanced Standard Care alone	Social Recovery Therapy plus Enhanced Standard Care	Enhanced Standard Care alone	Social Recovery Therapy plus Enhanced Standard Care	Enhanced Standard Care alone	Social Recovery Therapy plus Enhanced Standard Care	Enhanced Standard Care alone
Primary outcomes
Structured activity	11.3 (8.0)	11.3 (8.6)	21.4 (16.6)	22.3 (19.3)	22.4 (21.4)	27.7 (26.5)	24.3 (18.9)	32.4 (28.7)
Structured activity without childcare	11.0 (7.8)	11.2 (8.6)	20.3 (14.7)	22.2 (19.3)	21.1 (18.1)	24.9 (20.4)	23.8 (18.9)	26.6 (20.4)
Constructive economic activity	8.6 (7.1)	8.1 (7.0)	15.7 (14.3)	16.6 (15.9)	17.4 (19.9)	22.0 (24.5)	18.6 (16.7)	27.4 (28.0)
Secondary outcomes
Transition to psychosis*	-	-	12 (9.8%)	8 (7.5%)	6 (5.6%)	1 (1.1%)	3 (3.1%)	2 (2.5%)
CAARMS Symptom Severity	26.2 (16.5)	26.1 (15.9)	28.4 (21.5)	27.1 (18.7)	23.4 (21.0)	24.3 (18.9)	20.4 (21.3)	20.2 (19.4)
CAARMS Symptom Distress	52.5 (27.0)	52.1 (23.1)	47.5 (27.5)	44.7 (24.3)	43.4 (28.1)	39.7 (25.8)	42.8 (26.6)	31.0 (26.5)
Current Major Depressive Episode*	72 (52.2%)	65 (49.2%)	26 (21%)	33 (29.2%)	35 (29%)	26 (25.7%)	24 (22.6%)	18 (21.7%)
Major Depressive Disorder*	95 (68.8%)	93 (70.5%)	66 (52.8%)	55 (49.6%)	58 (47.5%)	43 (42.2%)	45 (42.5%)	28 (33.7%)
Current Social phobia*	62 (%)	54 (40.9%)	22 (40%)**	24 (53.3%)**	28 (52%)**	16 (39.0%)**	27 (59%)**	13 (36.1%)
Current Generalised Anxiety Disorder*	36 (%)	44 (33.3%)	11 (33%)	13 (41%)	10 (30.3%)	5 (46.5%)	13 (48%)	11 (42%)
BDI	30.4 (12.8)	30.3 (12.4)	18.6 (15.4)	19.9 (13.7)	19.2 (15.7)	19.4 (14.9)	18.0 (15.7)	17.5 (14.8)
SIAS	52.1 (14.1)	48.1 (16.1)	44.1 (16.9)	44.0 (15.6)	43.1 (17.7)	42.2 (17.7)	43.9 (17.6)	41.3 (17.4)
GAF	37.9 (5.6)	38.2 (5.5)	49.7 (15.8)	48.6 (14.9)	50.8 (18.0)	51.9 (17.4)	50.3 (17.2)	53.4 (16.2)
GAS	43.1 (7.3)	43.2 (7.5)	52.2 (15.2)	51.2 (14.1)	54.2 (16.0)	55.6 (17.9)	53.3 (17.6)	56.6 (16.6)
SOFAS	41.6 (7.6)	43.3 (7.0)	51.7 (15.5)	53.4 (16.5)	54.6 (17.3)	55.8 (19.4)	53.3 (18.1)	57.4 (19.4)
Other outcomes
BHS	13.4 (5.8)	12.7 (5.2)	9.2 (6.2)	9.1 (5.9)	9.5 (6.1)	9.5 (6.4)	9.6 (6.1)	7.8 (6.2)
AUDIT	5.0 (6.3)	5.2 (6.3)	4.6 (6.6)	4.4 (5.1)	4.6 (6.0)	4.5 (6.0)	3.5 (4.3)	3.7 (3.3)
DUDIT	3.6 (7.2)	3.9 (7.8)	3.1 (6.6)	3.8 (7.8)	2.6 (5.7)	3.4 (7.9)	2.1 (6.0)	3.3 (7.3)

Data are mean (standard deviation) unless otherwise specified. Structured activity and constructive economic activity outcomes are in hours per week, with secondary outcomes in continuous scores. *Data are frequency (percentage). ** For 9 months, 15 months and 24 months, for each diagnosis, the prevalence is based upon the total number at baseline with a positive diagnosis (discounting ‘missing’, or negative diagnosis at baseline). For log-transformed outcomes, the p-value comes from the log-transformed data analysis but estimates and confidence intervals are in the original units. SANS=Scale for the Assessment of Negative Symptoms. BDI=Beck Depression Inventory II. SIAS=Social Interaction Anxiety Scale. BHS=Beck Hopelessness Scale. THS=Trait Hope Scale. MLQ=Meaning in Life Questionnaire. Follow-ups were conducted between 30/11/2012 and 13/6/2019.

Participants allocated to SRT received a mean of 16.77 therapy sessions, with a range of 0 to 33. SRT adherence ratings demonstrated that 91 (68%) participants received full dose, 23 (17%) partial and 24 (18%) no dose (n=2 attended zero sessions). Seventy-five session tapes, at least one per therapist, were rated for competence. The mean CTS-R score was 47.24, with 97% of sessions rated above the competence threshold of 36. ESC provision was substantial in both arms. Over 80% of participants in both arms accessed NHS mental health services at trial entry, which continued for more than two-thirds throughout the intervention period, and for more than half throughout the trial. Between each assessment point, a mean of 38% ESC and 39% SRT participants saw a care co-ordinator or case manager on average 9-11 times, and 33% ESC and 25% SRT participants saw a psychological therapist on average for 7-12 sessions. An average of 66% of ESC and 72% of SRT participants saw their GP a mean of 3-5 times between each assessment point. An average of 19% of ESC and 14% of SRT participants saw a psychiatrist between each assessment point, on average 1-3 times. An average of 51% ESC and 54% SRT participants reported antidepressant use, and a substantial minority of other medications, between each assessment point. One third of participants in both arms reported employment support over the trial for a mean total of 11.3 (ESC; range 0.3-76.5) and 75.3 hours (SRT; range 0.5-842.4). Over 40% of ESC participants and 32% of SRT participants reported other youth, financial, educational, social, housing, statutory and telephone support services over the trial, for a mean total of 14.6 (ESC; range 0.2-225.0) and 7.9 hours (SRT; range 0.2-74.0).

Overall, 235 (87%) participants provided data for the primary outcome of weekly hours in structured activity at 15-months post-randomisation, with data missing for 13% participants (n=11 SRT plus ESC, n=24 ESC alone; see figure 1 and table 2). The primary intention to treat (ITT) analysis provided no evidence for the superiority of SRT plus ESC to ESC alone (table 3) in improving structured activity, nor in constructive economic activity. Interaction terms for ARMS status (At Risk Mental State for psychosis versus not) and social disability (low versus very low functioning) were non-significant. There was no evidence for the superiority of SRT plus ESC to ESC alone for structured activity at 9- or 24-months post-randomisation (table 3). At 24-months, there was weak evidence of greater structured activity in ESC alone (table 3). The per protocol (PP) analysis (table 3) was consistent with the ITT analysis at all timepoints. General linear models did not provide any evidence (table 4) for the superiority of SRT to ESC at any assessment point in transition to psychosis, attenuated psychotic symptoms, general mental health or other symptoms. There was no evidence (see supplementary information) of the superiority of SRT for negative symptoms or rates of diagnosable mood, eating, or somatoform disorders. It is notable that there were, in both trial aims, significant improvements were made from baseline to follow-up in time spent in structured activity, reduction in depression and anxiety symptoms and diagnoses, and improvements in other symptoms and markers of psychological wellbeing.

Figure 1. Participant flow diagram.

Table 3. Prespecified primary outcome analysis, and secondary time use outcome analysis, using Intention to Treat population and Per Protocol population.

	Intention to treat population		Missing data		Per Protocol population
Outcome and timepoint	Adjusted mean difference [95% Confidence Intervals], (Cohen’s d)	p value intervention versus control (log transformed p value)	Social Recovery Therapy plus Enhanced Standard Care (n=138) n (%)	Enhanced Standard Care alone (n=132) n (%)	Adjusted mean difference [95% Confidence Intervals], (Cohen’s d)	p value intervention versus control (log transformed p value)
Primary outcome
Structured activity at 9 months	-0.90 [-5.02, 3.21], (-.05)	0.67 (0.50)	12 (8.7)	17 (12.9)	-1.23 [-5.71, 3.25]	0.59 (0.45)
Structured activity at 15 months	-4.44 [-10.19, 1.31], (-.22)	0.13 (0.29)	11 (8.0)	24 (18.2)	-7.00 [-13.22, -0.78]	0.03 (0.19)
Structured activity at 24 months	-7.51 [-13.91, -1.12], (-.33)	0.02 (0.099)	25 (18.1)	40 (30.3)	-8.75 [-16.07, -1.42]	0.02 (0.059)
Structured activity without childcare at 9 months	-1.71 [-5.67, 2.26], (-.11)	0.40 (0.57)	12 (8.7)	17 (12.9)	-2.04 [-6.41, 2.34]	0.36 (0.52)
Structured activity without childcare at 15 months	-2.98 [-7.49, 1.53], (-.20)	0.19 (0.46)	11 (8.0)	24 (18.2)	-4.99 [-9.89, -0.08]	0.05 (0.31)
Structured activity without childcare at 24 months	-2.37 [-7.59, 2.84], (-.14)	0.37 (0.48)	25 (18.1)	40 (30.3)	-3.94 [-9.69, 1.82]	0.18 (0.26)
Secondary time use outcomes
Constructive economic activity at 9 months	-1.14 [-4.74, 2.45], (-.06)	0.53 (0.95)	12 (8.7)	17 (12.9)	-1.36 [-5.14, 2.42]	0.48 (0.80)
Constructive economic activity at 15 months	-4.44 [-9.88, 1.01], (-.21)	0.11 (0.085)	11 (8.0)	24 (18.2)	-6.92 [-12.72, -1.12]	0.20 (0.049)
Constructive economic activity at 24 months	-8.34 [-14.41, -2.27], (-.38)	0.01 (0.038)	25 (18.1)	40 (30.3)	-7.97 [-15.02, -0.93]	0.03 (0.073)

The 24-month assessment point was a late addition to the study protocol during the internal pilot at funder request and therefore reflects greater missing data.

For log-transformed outcomes, the p-value comes from the log-transformed data analysis but estimates and confidence intervals are in the original units.

Table 4. Prespecified secondary and other outcome analysis using Intention to Treat population.

	Intention to treat population		Missing data
Outcome and timepoint	Effect size [95% Confidence Intervals]	p value intervention versus control (log transformed p value)	Social Recovery Therapy plus Enhanced Standard Care (n=138) n (%)	Enhanced Standard Care alone (n=132) n (%)
Secondary outcomes
Transition to psychosis at 9 months*	1.30 [0.49, 3.44]	0.59	16 (11.6)	25 (18.9)
Transition to psychosis at 15 months*	7.33 [0.71, 76.25]	0.10	30 (21.7)	44 (33.3)
Transition to psychosis at 24 months	1.29 [0.20, 8.19]	0.79	40 (29.0)	51 (38.6)
CAARMS Symptom Severity at 9 months	2.26 [-1.92, 6.43], (.06)	0.29 (0.40)	21 (15.2)	28 (21.2)
CAARMS Symptom Severity at 15 months	0.29 [-4.35, 4.94], (-.05)	0.90	23 (16.7)	42 (31.8)
CAARMS Symptom Severity at 24 months	1.45 [-5.54, 8.44], (.01)	0.68	79 (57.2)	86 (65.2)
CAARMS Symptom Distress at 9 months	2.11 [-3.73, 7.95], (.11)	0.48	27 (19.6)	28 (21.2)
CAARMS Symptom Distress at 15 months	4.09 [-3.52, 11.70], (.14)	0.29	34 (24.6)	40 (30.3)
CAARMS Symptom Distress at 24 months	11.64 [1.29, 22.00], (.44)	0.03	80 (58.0)	85 (64.4)
Current Major Depressive Episode at 9 months*	0.71 [0.46, 1.11]	0.18	13 (9.4)	19 (14.4)
Current Major Depressive Episode at 15 months*	1.11 [0.72, 1.72]	0.65	16 (11.6)	31 (23.5)
Current Major Depressive Episode at 24 months*	1.04 [0.61, 1.79]	1.00	32 (23.2)	49 (37.1)
Major Depressive Disorder at 9 months*	1.07 [0.83, 1.37]	0.70	13 (9.4)	21 (15.9)
Major Depressive Disorder at 15 months*	1.13 [0.84, 1.51]	0.50	16 (11.6)	30 (22.7)
Major Depressive Disorder at 24 months*	1.26 [0.87, 1.83]	0.23	32 (23.2)	49 (37.1)
Current Social phobia at 9 months*	0.75 [0.49, 1.15]	0.23	7 (5.1)	9 (6.8)
Current Social phobia at 15 months*	1.33 [0.84, 2.11]	0.30	8 (5.8)	13 (9.8)
Current Social phobia at 24 months*	1.63 [0.99, 2.67]	0.05	16 (11.6)	18 (13.6)
Current Generalised Anxiety Disorder at 9 months*	0.75 [0.41, 1.37]	0.46	3 (2.2)	8 (6.1)
Current Generalised Anxiety Disorder at 15 months*	1.34 [0.69, 2.61]	0.44	4 (2.9)	11 (8.3)
Current Generalised Anxiety Disorder at 24 months*	1.14 [0.63, 2.06]	0.79	9 (6.5)	18 (13.6)
BDI at 9 months	-1.28 [-4.83, 2.26], (-.09)	0.48	24 (17.4)	32 (24.2)
BDI at 15 months	-0.32 [-4.06, 3.42], (-.01)	0.87	25 (18.1)	38 (28.8)
BDI at 24 months	1.93 [-2.22, 6.08], (.03)	0.36	41 (29.7)	51 (38.6)
SIAS at 9 months	-2.56 [-6.13, 1.01], (.01)	0.16	23 (16.7)	29 (22.0)
SIAS at 15 months	-0.45 [-4.84, 3.95], (.05)	0.84	23 (16.7)	38 (28.8)
SIAS at 24 months	1.48 [-3.50, 6.45], (.15)	0.56	39 (28.3)	49 (37.1)
GAF at 9 months	1.57 [-2.12, 5.27], (.07)	0.40	17 (12.3)	26 (19.7)
GAF at 15 months	-0.93 [-5.24, 3.38], (-.06)	0.67	21 (15.2)	37 (28.0)
GAF at 24 months	-2.87 [-7.49, 1.76], (-.19)	0.22	36 (26.1)	51 (38.6)
GAS at 9 months	1.02 [-2.51, 4.56], (.08)	0.57	17 (12.3)	26 (19.7)
GAS at 15 months	-1.72 [-5.95, 2.51], (-.08)	0.43	21 (15.2)	35 (26.5)
GAS at 24 months	-3.63 [-8.40, 1.14], (-.19)	0.14	38 (27.5)	50 (37.9)
SOFAS at 9 months	0.24 [-3.37, 3.84], (-.11)	0.90	17 (12.3)	26 (19.7)
SOFAS at 15 months	0.60 [-3.64, 4.84], (-.07)	0.78	20 (14.5)	35 (26.5)
SOFAS at 24 months	-2.05 [-6.91, 2.81], (-.22)	0.41	38 (27.5)	50 (37.9)
Other outcomes
BHS at 9 months	-0.17 [-1.70, 1.36], (.02)	0.83	28 (20.3)	33 (25.0)
BHS at 15 months	-0.17 [-1.80, 1.47], (.00)	0.84	22 (15.9)	39 (29.5)
BHS at 24 months	1.40 [-0.34, 3.14], (.29)	0.12	40 (29.0)	52 (39.4)
AUDIT at 9 months	0.52 [-0.67, 1.71], (.03)	0.39 (0.92)	23 (16.7)	29 (22.0)
AUDIT at 15 months	0.63 [-0.69, 1.95], (.02)	0.35 (0.46)	22 (15.9)	35 (26.5)
AUDIT at 24 months	0.24 [-0.68, 1.16], (-.05)	0.61 (0.27)	36 (26.1)	49 (37.1)
DUDIT at 9 months	-0.71 [-2.02, 0.61], (-.10)	0.29 (0.42)	19 (13.8)	28 (21.2)
DUDIT at 15 months	-1.05 [-2.54, 0.45], (-.12)	0.17 (0.46)	19 (13.8)	39 (29.5)
DUDIT at 24 months	-1.36 [-2.86, 0.14], (-.18)	0.08 (0.01)	34 (24.6)	47 (35.6)

^*Effect sizes are Odds Ratio (OR).

^**Effect sizes are Relative Risk (RR).

All other effect sizes are given as adjusted mean differences, with Cohen’s d additionally provided in parentheses. The 24-month assessment point was a late addition to the study protocol during the internal pilot at funder request and therefore reflects greater missing data.

Primary outcome missing data was 11% at 9-months and 24% at 24-months post-randomisation. Missing data was greater for secondary outcomes across timepoints (table 2). Moreover, there was evident differential missingness and a bias towards greater attrition in the ESC alone arm throughout the trial. Missing data modelling was performed using full information maximum likelihood and multiple imputation approaches. The missing data analysis was consistent with the ITT analysis and provided no evidence for the superiority of SRT plus ESC compared to ESC alone on any outcome.

There were 84 adverse events and 83 serious adverse events during the trial, affecting 59 and 42 individuals respectively. More serious adverse events, for example medication overdose, were reported by SRT plus ESC participants (n=53) compared to ESC participants (n=30). However, events became very similar when adjusting for only those reported at trial assessments and excluding those reported to SRT therapists; SRT plus ESC n=36, ESC alone n=30. No events were attributable to the trial.

For health economic outcomes, the mean total intervention cost per SRT participant was £3268.94 (SRT plus ESC was estimated at £5927.73) versus £2420.61 for ESC alone. The mean incremental cost for SRT was estimated to be £3,910.59 (£2,708.32-£5,112.86), compared to ESC, with a quality-adjusted life-year gain of 0.001 (-0.099—0.10). Therefore, SRT was not estimated to be cost-effective.

Discussion

The aim of this trial was to determine the clinical and cost-effectiveness of adding Social Recovery Therapy (SRT) to Enhanced Standard Care (ESC), compared to ESC alone, for young people with social disability and severe and complex mental health problems. We found no evidence of the superiority of SRT as adjunctive to ESC in the primary outcome of weekly hours in structured activity at the primary 15-month endpoint or at 9- or 24-months post-randomisation. We found no evidence that SRT was superior to ESC in secondary or other outcomes at any timepoint. SRT was not estimated to be cost-effective.

On some outcomes, including negative symptoms at 15-months and structured activity at 24-months post-randomisation, there were mean differences in favour of ESC alone. However, these findings were inconsistent and rarely approached statistical significance. For other outcomes, including depression and anxiety diagnoses and drug use, there was weak evidence in favour of SRT plus ESC. Similarly, these results were inconsistent and not statistically significant.

There were very large gains made in both trial arms across primary and secondary outcomes. In both trial arms, there was an average gain of 11 hours in structured activity at 15-months postrandomisation, which constitutes almost threefold a clinically meaningful effect. There was more than 50% improvement in the prevalence of diagnosable depression, social phobia, panic disorder and agoraphobia in both groups, and large gains in self-reported depression, social anxiety, hopelessness, schizotypy, and drug and alcohol disorders. This was surprising as only a minority of young people with complex emerging problems show reliable gains following specialist youth mental health service provision(4). Current participants had greater symptomatology than this prior study and, therefore, more change may have been possible. However, current participants had been experiencing significant difficulties for at least 6 months and were accessing treatment as usual, thus change without specialist intervention was unexpected. Nonetheless, our results support those of the IMPACT adolescent depression trial(27), in which optimised case management (i.e. including, as per this trial, psychological, occupational and practical support) appeared equally as effective with and without the addition of different psychotherapies. Moreover, recent studies demonstrate that some individuals at elevated psychosis risk may show symptomatic and functional improvement over time(28). The present sample were heterogenous with respect to symptoms and comorbidities and, therefore, may have included participants who naturally recovered in addition to subgroups who responded well to shorter or longer-term, specialised interventions(29).

Anticipating that standard care might be limited and inaccessible, we provided thorough assessment feedback and a best practice referral guide. The data show that comprehensive packages of evidencebased interventions of case management, psychological therapy, medication and employment support were delivered to both arms of the trial, within three youth mental health centres of excellence. It is important that the large gains made in social and clinical recovery occurred in the context of the this very active and comprehensive provision, which constituted optimal care according to NICE guidelines. In the context of such comprehensive evidence-based care, what the trial perhaps shows is that providing further adjunctive specialised social recovery therapy is not required. Further research is warranted in understanding how benefits occurred and the factors associated with improvement. The implication for services is to try to actively engage, and deliver comprehensive assessment and treatment to maximise outcomes for this often-neglected group.

Our qualitative process evaluation found that SRT was experienced positively by the participants interviewed; that SRT was challenging but beneficial, and provided participants with a positive therapeutic relationship and specific tools needed to pursue social recovery goals(21). Participants in both arms described benefits of trial involvement; experiencing the assessment process as facilitating self-reflection and highly valuing contact with warm, empathic assessors(20). SRT was contrasted to standard care, which participants described as too limited(21). It is notable that trial assessment procedures were experienced by participants as facilitating hope(20,21) and may have increased standard treatment engagement alongside our deliberate attempts to encourage providers to offer comprehensive treatment packages. Our previous SUPEREDEN3 trial(19) found that SRT as adjunctive to EIP was superior in improving social and clinical recovery. Thus, adjunctive SRT may become necessary and effective only following transition to psychosis, and moreover amongst a group characterised by greater homogeneity, i.e. male gender, persistent and severe symptoms and social disability despite prior provision of specialist mental health services, such as in the SUPEREDEN3 trial(19). This is in keeping with the plasticity of the adolescent brain, which whilst conferring heightened vulnerability, provides greatest receptivity and malleability to resilience-enhancing factors, thus meaning adolescence is a period of greatest therapeutic gains(30). Further research to unpick the characteristics which distinguish persistence of social disability in psychosis, as compared to what appears from this trial to be greater responsivity to treatment in the absence of psychosis but equivalent severity and complexity, is needed.

As evident at baseline, trial participants were extremely withdrawn and severely symptomatic. The inclusion of this group in an intervention trial was challenging. We made considerable efforts to engage and retain participants but despite this, there was marked missing data with greater disengagement in the control arm. There was an over-representation of males in the SRT plus ESC arm. Sex was not a stratifier, nor was any related analysis planned a priori, and sex imbalance could have biased estimates. Nonetheless, the ITT analysis to primary outcome was regarded as appropriate and within prespecified limits against bias and alternative missing data models, full information maximum likelihood and multiple imputation, were used to support this.

Future research should aim to further explore the factors associated with youth mental health problems that are persistent and resistant to standard treatment(4,5), and the characteristics and mechanisms associated with good response to existing packages. Future research should identify how to optimise standard care depending on need and how to implement optimal combinations of evidence-based interventions for young people with complex problems(4,5). This may involve the consideration of stepped-care style approaches to identify young people who are more treatmentresistant and require longer-term specialist social recovery intervention(4,5). Existing research suggests that patients with severe and complex problems struggle to access interventions(4,5).

However, this study shows that, even with very severe social disability and complex mental health problems, young people can make very significant improvements if comprehensive packages of evidence-based care are provided. Such packages include detailed engagement and assessment, and access to psychological therapies and vocational support, alongside medical and social interventions. The gains obtained by such provision have been shown to be large in this study, and in this context, the addition of specialised social recovery therapy does not provide superior social or clinical recovery, nor is it cost-effective. The message of this trial is to recommend equitable provision of optimised evidence-based care packages for clinical and social recovery within services which are appropriate and accessible for young people. Participants in the trial process evaluation emphasised the importance of motivation and self-agency in social recovery(20,21) and delivering this care to young people in the context of hopefulness appears essential.

Research in context.

Evidence before this study

Scopus was searched on the 15^th October 2020 using the terms ‘severe/complex/serious/co-morbid mental’ and ‘social recovery/social functioning/functional outcome’ and ‘young/youth/adolescents’ and ‘psychological/psychosocial’ and ‘intervention’. There were no search restrictions made. Eighteen records were identified. Twelve studies were irrelevant due to a focus on schizophrenia, psychosis, addiction or on middle or older adults. One record was the protocol(1) for this trial and another a position paper(2) authored by this group. Four remaining studies were relevant. The first is a systematic review focused on psychosis prevention(3). This study found no evidence in support of any preventative intervention over any other, or compared to any control arm, for people with clinically elevated risk of psychosis; either with respect to psychosis prevention or other mental health or functional outcomes. Interventions included pharmacological and non-pharmacological interventions, for example Cognitive Behavioural Therapy. Two studies investigated outcomes for young people with subthreshold mental health problems attending a specialist youth mental health service. The first indicated high heterogeneity in the clinical outcomes of this group following early intervention in the youth mental health service(4). The second study indicated that young people with attenuated syndromes had greater need for intervention than those without(5). Attenuated syndromes are those in which symptoms are subthreshold in frequency or severity compared to what would warrant clinical diagnosis. The attenuated syndrome group showed a reduced, albeit positive, treatment response. Finally, one uncontrolled study provided students with mild self-reported depression or subclinical psychotic symptoms with a brief novel group workshop-based intervention targeting clinical symptoms and resilience(6). The intervention appeared significantly effective; however, the student sample was not a clinical sample and there was no comparator.

Added value of this study

This study complements the existing literature in demonstrating the lack of evidence for a benefit in social functioning to specialist individual psychosocial intervention, compared to enhanced standard care. Existing evidence suggests provision of active standard care and more specialist intervention do not appear to differ with respect to social recovery, psychosis prevention, general mental health and psychological functioning outcomes for young people with severe and complex mental health problems. Compared to a prior systematic review which included studies involving only young people at elevated risk of psychosis(3), the current study extends the focus to young people with severe and complex mental health problems who both did and did not have elevated risk of psychosis. The present study confirmed that both enhanced standard care and specialist social recovery therapy were associated with very large effect size treatment gains, on average, across social and clinical recovery for this broader group.

Implications of all the available evidence

The implications of the available evidence at present suggest that provision of good quality existing standard care, aligned with evidence-based NICE guidelines, appears sufficient to engender positive outcomes, on average, for this group. Good quality standard care includes comprehensive packages of psychosocial interventions and medication where indicated, such as within child and adolescent or early intervention in psychosis mental health services. The best outcomes derive from services which provide the full range of social, psychological and medical interventions according to need. At present no adjunctive extra highly specialist intervention has yet demonstrated gains beyond those obtained by existing comprehensive packages of evidence-based interventions. Further research is needed regarding individualised care, however, in the context of the high heterogeneity of young people with severe and complex mental health problems. Some subgroups do not respond or engage with any intervention and remain symptomatically and socially disabled. New studies are required to explore identification of clinically and functionally meaningful high-risk subgroups within the broader complex and severe population. New studies are additionally needed to establish the necessary and sufficient components of optimal intervention for these subgroups to reliably improve social and clinical recovery and prevent transition to more severe problems such as psychosis. Methodological innovation is additionally required to better manage trial attrition and differential missingness in the context of complexity, youth, and high social withdrawal.

Data availability statement

The data that support the findings of this study are available from the corresponding author, CB, upon reasonable request.