Managing unusual sensory experiences for people with an at-risk mental state for psychosis

As this is a feasibility trial, feasibility outcomes for the delivery of a large-scale randomised controlled trial are of key importance. The primary outcome of this feasibility trial is the ability of the trial to recruit 88 participants, who reflect the diversity within the region, meet study inclusion criteria over the 9-month recruitment period, and complete assessment measures collected at baseline, post-intervention (12 weeks post-randomisation) and follow-up (20 weeks post-randomisation), until all participants complete the follow-up assessment or withdraw.

The researchers will use a traffic light system to inform progressions criteria (above 80%: green; 60–79%: amber; below 60%: red) and will use a consort diagram to plot progression through the trial and will review at end of the trial data collection (final assessment of final participant).

1. Referral rate. The researchers will check the percentage of potentially eligible clients who are referred. The date used to inform recruitment rate suggested quite different rates of eligibility across the two sites (65% in TEWV and 95% in CNTW).
2. Recruitment rate. The researchers calculated that they should be able to recruit 9.8 pcm. They will monitor across the study and green would be achieving 80%, therefore 7.85 pcm.
3. Reasons for declining participation. The non-consent group will be sensitively asked to share reasons for non-participation via the NIHR Participant Research Experience ‘Okay to say No’ (anonymous) questionnaire (https://myresearchexperience.com/), which asks an open question about the reasons for deciding not to take part, along with basic demographic information (age and ethnicity). This will happen at the point the potential participant declines to participate.
4. Allocation compliance rate and attrition rate. We will monitor this through our CONSORT diagram and review at the end of the trial, using our traffic light system.
5. Appropriateness and integrity of treatment protocols. Therapists will be asked to complete adherence checklists for each session. Adherence checklists will be specific to the intervention (MUSE/Supportive Psychotherapy). With consent, each session will be audio-recorded to enable an independent review of a random 10% sample to ensure fidelity to protocol within and across sites. Treatment fidelity will be assessed by the site PI or Co-Investigator/Clinical lead/Supervisor who is not a trial therapist.
6. Completion rates of measures and psychological tasks. This will be provided by the statisticians at the end of the analyses and assessed using the traffic light system for progression.
7. Time needed to collect, clean and analyse data. The statisticians have been allocated 3 months to clean and analyse the data at the end of the study. They will inform us of the time required for this task.
8. Robust estimates of effect size (primary/secondary outcomes) to inform sample-size calculations for future trials. The effects will be estimated using generalised linear mixed-effect models with the appropriate distribution and link function. Normal distributions with identity link will be used for continuous outcomes, and negative-binomial distributions with log link for count data outcomes. All binary or categorical outcomes will be analysed using generalised estimating equations (GEE). The mixed-effects models and GEE account for the repeated measurements per participant over the follow-up time points. All models will be adjusted for treatment arms and stratification variables. The mixed model approach taken will allow identifying the individual effect of the two interventions w.r.t their baseline, as well as the difference in their effects through an interaction parameter of time and intervention. This can be considered as a model-based difference-in-difference analysis.
9. Analysis of components of TAU at each site. Details of all treatment received in both groups will be recorded using the Client Service Receipt Inventory CSRI (mental health) questions 4 to 5, amended for this trial to add specific questions to measure receipt of relevant interventions in both arms for the duration of the study.

Qualitative data will inform the researchers' understanding of participants’ subjective experiences of the intervention and its impact on their understanding of their voice-hearing experiences (e.g. changes in beliefs about origin), along with the acceptability of the intervention (including experiences of the quality of intervention and participant responsiveness) and trial procedures for participants and therapists. Audio recordings will be transcribed and analysed (in NVivo software). Interview transcripts will be analysed using thematic analysis allowing a transparent, replicable and robust process and demonstration of reflexivity and quality. Transcripts will be coded by two researchers until coding reliability is established; coding will then be conducted by one researcher, with reliability checks by the qualitative lead. Data will be extracted into a framework matrix, summarising data by category from individual transcripts, with quotations selected as illustrative exemplars. Initial findings from the qualitative analyses will be presented to LEAP for feedback on interpretation.

The treatment delivered in this intervention aims to improve functioning and reduce the distress associated with hallucinations. Accordingly, candidate primary outcome measures that will be investigated for suitability for future trials are global functioning, as measured on the SOFAS, and hallucinations measured using the PSYRATS hallucination scale, with attention to subscales of interest: distress and attribution. The effect of the interventions on outcomes will be estimated from the change from baseline as well as changes in the mean scores in each trial arm. The feasibility of measuring caseness and caseness change, or clinically meaningful levels of response will be explored.

1. Functioning assessed using the Social and Occupational Functional Assessment Scale (SOFAS)
2. Mental State assessed using the Psychotic Symptom Rating Scale (PSYRATS) hallucinations total
3. Hallucinations assessed using the Psychotic Symptom Rating Scale (PSYRATS) distress
4. Attribution assessed using the Psychotic Symptom Rating Scale (PSYRATS) attribution

These measures are collected at three timepoints; baseline, post-treatment (12 weeks post-baseline), follow-up (20 weeks post-baseline).