Treatment effect modifiers of cognitive behaviour therapy in people with psychosis: an individual participant data meta-analysis of RCTs.

Background: Cognitive-behavioural therapy is a recommended intervention for the treatment of schizophrenia and related psychoses, but there is considerable uncertainty on whether its effectiveness is moderated by patient characteristics and/or intervention characteristics. Objective(s): To identify treatment effect modifiers of cognitive-behavioural therapy in people with schizophrenia spectrum diagnoses. Design: An individual participant data meta-analysis of randomised controlled trials comparing cognitive-behavioural therapy to treatment as usual or control active psychosocial control interventions. Setting: Community and inpatient settings. Participants: Individuals with schizophrenia spectrum diagnoses. Interventions: Cognitive-behavioural therapy, as defined by the criteria outlined in the National Institute for Health and Care Excellence guideline on treatment and management of schizophrenia in adults. Main outcome measures: Overall symptom change as measured by assessments of overall psychotic symptom severity (e.g. the Positive and Negative Syndrome Scales). Data sources: Corresponding authors of 110 trials identified from the database searches conducted as part of a related aggregate data meta-analysis in February 2018 (later updated in January 2019) were invited to share their trials' individual participant data, and additional trial documentation, when available, pertaining to relevant individual participant data metadata, statistical analyses plans and characteristics of the cognitive-behavioural therapy interventions evaluated in their eligible trials. Review methods: Reports of retrieved and unretrieved trials were assessed using the Cochrane Risk of Bias tool. Data were cleaned and standardised to allow pooling and analysis. We conducted a series of two-stage individual participant data random-effect meta-analyses across four treatment comparisons: cognitive-behavioural therapy versus treatment as usual; cognitive-behavioural therapy versus other psychosocial interventions/active comparisons (active control psychosocial interventions); cognitive-behavioural therapy integrating additional elements from other therapies ('cognitive-behavioural therapy+') versus treatment as usual; and cognitive-behavioural therapy+ versus active control psychosocial interventions. Treatment by covariate interaction analyses were carried out to examine potential treatment effect modifiers, including participants' demographic characteristics (age, gender, ethnicity), clinical characteristics (illness duration, phase of illness, duration of untreated psychosis, initial severity of psychotic symptoms and affective symptoms), and specific intervention characteristics (treatment duration, number of therapy sessions, level of therapists' training/competence, use of manualised interventions, formulation-based interventions; individual vs. group interventions). Results: A total of 53 trials were retrieved. Of these, 27 trials ( Limitations: Only 54% of the individual participant data requested were provided by data owners, and there is considerable heterogeneity in the features of the cognitive-behavioural therapy interventions included in this evidence synthesis. Conclusions: The effectiveness of cognitive-behavioural therapy for overall symptom change in this patient group is not significantly affected by the covariates examined in this individual participant data meta-analysis. Cognitive-behavioural therapy should continue to be offered equally to service users irrespective of their demographic or clinical characteristics. Future work: Other potential avenues to explore moderators of cognitive-behavioural therapy efficacy are suggested, including the fine-grained analysis of specific intervention components and the added value of interventionist-causal paradigms. Study registration: This study is registered as PROSPERO CRD42017060068. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/187/05) and is published in full in