The CIRCuiTS study (Implementation of cognitive remediation in early intervention services): protocol for a randomised controlled trial

Schizophrenia is a relatively common disorder with a lifetime risk of around 1% [1]. It typically has an onset in late adolescence or early adulthood, so can derail the academic, interpersonal and employment achievements that prepare a person for adult roles and responsibilities [1]. It is also associated with an average loss of life-span of up to 20 years [2], poor employment prospects and difficulty in achieving satisfying social relationships. Poor prognosis is established soon after illness onset, with estimates of sustained social and occupational recovery being only 17–25% in the first 5 years [3]. Although positive symptoms (delusions and hallucinations) are a hallmark of a diagnosis of schizophrenia, cognitive dysfunction is apparent prior to the onset of psychosis and remains unchanged despite symptom remission [4, 5]. Poor cognition in people with a diagnosis of schizophrenia is a key predictor of poor functional outcome [6, 7] and impairments are noticeable in about 96% of all outpatients [8]. It is cognitive function at psychosis onset, and not symptom profile or response to treatment, that most strongly predicts social and occupational functioning 4 years later [9]. Cognitive difficulties also limit the rate of improvement using evidence-based rehabilitation, so that those who have the most difficulty will gain least [6]. Interventions that can boost cognition or maintain cognitive reserve would be beneficial, as these improvements are likely to have wide-ranging effects on service outcomes.

Owing to the potential for chronicity and morbidity, the economic burden of schizophrenia is immense. In the UK, it was estimated as £19b in 2012, and for each patient each year as £60k in societal costs and £36k in public sector costs (Schizophrenia Commission 2012 [10]) with similar figures found in the USA [11]. Much of the social burden is due to lost employment, housing and benefits [12]. New UK mental health policies, such as ‘No health without mental health’ [13], stress the need for early intervention to make long-lasting differences in people’s lives. With such a poor prognosis and high costs as well as personal burden, it is vital to explore whether new therapies can improve the recovery trajectory and thus decrease costs. Embedding cognitive treatments early, as in early intervention services (designed for clients who undergo intensive case management over the first 3 years of illness), may confer potentially long-lasting benefits.

Cognitive remediation therapy (CRT) was developed to address cognitive problems in people with schizophrenia. The Cognitive Remediation Experts Workshop in 2012 [14] defined it as ‘an intervention targeting cognitive deficit using scientific principles of learning with the ultimate goal of improving functional outcomes’ (p. 1). The largest meta-analysis (> 2000 participants in 40 studies) demonstrated that CRTs provide durable benefits in global cognition (effect size, 0.45) and functioning (Cohen’s d effect size, 0.42) [15] against any control group. New evidence and systematic reviews were taken into consideration by the Scottish Guideline Network for Healthcare Improvement Scotland [16] (extending the National Institute for Health and Care Excellence (NICE) guidelines of 2014 [17]) and CRT is now recommended in Scotland. Because of this wealth of evidence, other countries, such as Australia, Italy and Japan, and the New York State mental health services now include it in their guidance.

Cognitive remediation experts [14] recommend that ‘the effect on functioning is enhanced when provided in a context (formal or informal) that provides support and opportunity for extending everyday functioning’ p. 1. This is based on evidence that CRT boosted outcomes in other evidence-based therapies [18, 19]. One study, based in an early invention for psychosis services, also demonstrated that CRT can halve the number of cognitive behaviour therapy sessions needed for the same symptom reduction, reducing costs [19]. Early intervention services provide multimodal therapies, as well as contact with social and employment services. They therefore offer formal and informal opportunities for the translation of gains, as well as the potential to boost CRT outcome and improve the potential for changing recovery trajectories and sustaining benefits.

Cognitive remediation studies in younger people demonstrate acceptability and benefit in the short and longer term for cognitive and functional domains [20‐22]; secondary analyses show greater gains for younger participants [23, 24]. There is ample evidence of biological and cognitive effects in schizophrenia, in which loss of brain grey matter [25, 26] and network disconnectivity occurs early in the disorder, but also evidence that CRT offers neuroprotective effects against grey matter loss [27] and improves brain activation [28]. As CRT has been shown to be effective for younger people and has the potential to improve functioning, it may be most beneficial if interventions are delivered at the earliest opportunity. There was optimism that early intervention services would have longer-term benefits but, despite quick access to multimodal treatments, it has been difficult to demonstrate that short-term improved outcomes were durable [29‐31], although individual studies show better results [32]. On the whole, the results are like those of Bertelsen and colleagues [33] that, irrespective of receiving early intervention services, 60% of service users were neither working nor studying 5 years after psychosis onset. Clearly the current ingredients of recovery-focused treatments are not achieving their full potential for later function. This trial has also taken a recovery-focused approach and highlights those outcomes of relevance to an individual. Our primary outcome measure is, therefore, the important functional goal as chosen by the participant.

Cognitive remediation therapy is an evidence-based intervention but what is not obvious is the mode of implementation necessary and who would benefit most from different therapeutic modalities. Cognitive remediation therapies have been provided with high therapist involvement or very little, and at different intensity levels. We therefore developed the arms of the trial to represent the most frequently used implementation methods. The first is an intensive therapy that has previously been used by our team [34], which depends on continuous therapist support. The second arm is one adopted in many studies, where treatment is provided in a group with therapeutic support [35]. We have shown that our current therapy is suitable for such a group-intervention [36] approach. The final arm is one that depends on more independent access to therapy and has been used in several trials with differing effects [37, 38]. The main differences between these implementation methods is the level of therapist support and therefore the costs of implementation, with the most independent being the cheapest. Although the presence or absence of therapist support did not affect cognitive outcomes [14], therapist support has been shown to have tangible effects [39] and service users have positive views about therapists being present during therapy [40, 41]. Balancing the cost of the service, service user preferences and outcomes has not been tested as there have been no direct comparisons using the same cognitive remediation programme with differing levels of therapist support. The question of what is the best implementation method therefore has clinical equipoise. Cognitive remediation therapies have also generally been tested in single-centre studies so the effect of differing background services on outcomes has also not been tested. Therefore, this large, multicentre trial was developed, with the main aim of determining the best way of introducing CRT for psychosis into UK National Health Service (NHS) early intervention services in order to optimise individual functional outcomes and costs.

We consulted people with experience of using mental health services at every stage of trial development as well as clinicians and carers, mindful of the finding of Ennis and Wykes [42] that patient involvement is associated with study success. For example, clinicians do not routinely introduce the idea of cognitive difficulties at psychosis onset to service users. To address this sensitive issue, we consulted service users, carers and mental health clinicians through focus groups and developed three study leaflets, which were approved by an ethics committee, to accompany the participant information sheet. We also consulted the National Institute for Health Research Biomedical Research Centre Young Person’s Mental Health Research Advisory group about the design, wording of the protocol, participant information sheet, consent form and other promotional material for the trial.

Research protocol, version 1.3, 1 March 2017.

Recruitment start date, 1 June 2017; predicted recruitment end date, 1 January 2020.