Title: Clinical and cost effectiveness of aphasia computer therapy compared with usual stimulation or attention control long term post stroke (CACTUS)
Funder: Department of Health and Social Care

Abstract: Design A pragmatic randomised controlled trial (RCT) to compare outcomes for people with persistent aphasia using computerised speech and language therapy(SLT)at home with those having usual care or attention control. A feasibility phase with a review of progression criteria half way through the recruitment phase is planned. Setting Computer therapy exercises will be provided in participants’ own homes. Recruitment, assessment and tailoring computer exercises will be coordinated by 20 Speech and language therapy (SLT) departments across the UK. Target population People presenting with aphasia at least 4 months post stroke with no upper limit. Health technologies being assessed Participants will be supported to self manage continued daily aphasia therapy exercises using available computer software for 6 months. Computer exercises will be tailored to individual needs by a SLT (up to 4 hours per patient) followed by monthly volunteer visits for support. Available software is subject to improvements over time, however the underlying therapy principles will remain the same. Measurement of costs and outcomes All outcome measures will be made at baseline, 6, 9 and 12 months by blinded research speech and language therapist assessors at each site. Primary outcomes: 1.The change in the number of words (of personal relevance to the participant) named correctly at 6 months will be measured by a picture naming task. This was successfully used to measure change in impairment in the pilot carried out by this team. 2.Improvement in functional communication will be measured by blinded ratings of video recorded conversations between a SLT and participants, using the activity scale of the Therapy Outcome Measures, at 6 months, as validated in the ACTNoW study. Conversations will be structured around topics of personal relevance to participants. Key secondary Improvement in patient perception of communication will be measured using the COAST - a patient reported measure of communication participation and related quality of life, validated for evaluating SLT interventions in the HTA ACTNoW project. The primary and key secondary endpoints will be analysed using a Hochberg testing procedure which allows for an investigation of all three endpoints whilst maintaining the overall Type I error at 5%. Cost effectiveness A cost-utility analysis will be undertaken from the NHS and personal social service perspective. A societal perspective will be included due to volunteer involvement. Intervention and SLT time costs will be estimated for individuals. The EQ5D will be administered at all time points and combined with standard valuation sources to measure quality adjusted life years (QALYs) gained in each group. An accessible version of the EQ5D, tested in the pilot study, enables scores to be elicited directly from patients with aphasia. This will be administered alongside the standard version completed by carers (where available) by proxy. EQ5D and CarerQoL scores will also be elicited from carers. An economic model developed alongside the pilot study will be updated. Differences between costs and QALYs in the 3 groups will be described and the incremental cost effectiveness ratio(ICER)will be calculated. Other secondary Evidence of therapy effect will also be measured by repeating all the above measures at 9 and 12 months from baseline. Generalisation of therapy to retrieval of untreated items will be measured by naming words from the Naming test within the Comprehensive Aphasia Test. Use of the target words in conversation Carer perception of communication participation will be measured using the Carer COAST. Adverse events will be recorded through patient/carer diaries (death, subsequent stroke, hospitalisation, negative effects of the computer treatment) Health service use will be evaluated through SLT diaries for all groups. Analysis Primary and key secondary endpoints will be analysed using a Hochberg testing procedure. Significance will be declared if improvements in both functional conversation and word retrieval at 6 months are significant at the 5% level or if either comparison is significant at 2.5%. COAST ratings will be assessed at 5% if both conversation and word retrieval are significant. Sample size The sample size is 285 patients(95 per arm) which is the maximum sample size estimate across the two primary and key secondary endpoints for 90% power and a two sided significance level of 5%. Based on recruitment rates in the pilot, 20 sites will be required. Sample size calculation: Assessment of conversation - effect size estimate is 7.2 and SD 13.5 (with a correlation between baseline and outcome of 0.5 previously observed). Improvement in word retrieval - effect size is 10% and a standard deviation (SD) of 17.38% from an analysis of covariance (based on pilot results). Patient rated improvement - effect size is 0.45 of an SD (with an assumed correlation between baseline and outcome of 0.5). These calculations take in to account an expected 15% drop out rate based on pilot results. Timetable Months 1-6: Ethics permission, site recruitment (feasibility assessment) creation of CRFs/database 7-14: local R&D approval, site staff recruitment and training, site initiation visits 8-16: recruitment and training of volunteers/SLT assistants at each site (staggered start for 20 sites) 11-31: Patient identification, screening and recruitment for 15 months at each site (staggered start). Recruitment rate estimated from the pilot study was 1 participant per month. Computer exercise tailoring and baseline measures. Month 22 review of progression criteria. 17-43: Follow up visits and outcome measures. 18-44: Data cleaning/validation 45-50: Site closure, database lock and data analysis 51-54: Report writing and dissemination of results Team expertise The research team comprises researchers with clinical skills in speech and language therapy, statistics, health economics, and trial management. The clinical trials research unit are represented in the team. People with aphasia and their carers form an advisory panel. Team members worked together on an RfPB funded pilot study of this intervention. Expected Value of Information analyses undertaken alongside our pilot study demonstrated the value of obtaining further information to be very high (Expected value of perfect information approx £37 million).

Lay abstract: Aphasia is a communication disorder often caused by stroke. It affects the ability to understand, talk, read and write. The HTA commissioning brief called for research into speech & language therapy for people who have communication problems for 4 months or longer after their stroke. Speech and language therapy is usually only offered for the first few months after stroke. In these first months, many people are medically unwell, tired and may be concentrating on competing demands of recovering physical skills. This may reduce their capacity to focus on speech therapy intensively. Many people do not meet their potential for recovery over this time period. As a consequence of persisting aphasia people find it difficult to take part in everyday activities, communicate with family/friends or work, often leading to depression. This reduces quality of life and increases costs to health and social services. There is evidence to suggest that aphasia can continue to improve if therapy is provided intensively in the longer term. Opportunities for therapy in the later stages after stroke would enable people to access therapy when their health has improved, and as communication needs change over time. Providing intensive face to face therapy in the long term is costly and difficult to achieve with competing demands on limited therapy resources. We wish to evaluate self managed computerised therapy exercise practice for persistent aphasia, tailored by speech and language therapists and supported by volunteers or speech and language therapy assistants. We carried out a pilot study evaluating this approach with 34 people with persistent aphasia. They were randomly assigned to using available computer software designed for treating aphasia, or usual long term care (most frequently this was social support). On average, people with aphasia practiced their speech exercises on the computer independently for 25 hours over 5 months (20 minutes, 3 times a week). The findings indicated that self managed computer therapy supported by volunteers could help people with aphasia to continue to practise, improving their vocabulary and their confidence talking. Patients and carers found it an acceptable alternative to face to face therapy. Self managed computer therapy could improve the quality of life of people with persistent aphasia, reducing costs to the NHS and society. A large randomised controlled trial (RCT) to compare aphasia computer therapy with usual care in the long term post stroke is now proposed. This builds on our published pilot work which provided information on how long it would take to recruit enough people to the study, how to provide the proposed therapy, and how to measure whether it was successful. It will be carried out by speech and language therapy departments across the UK with enough participants to provide robust findings. Twenty departments are needed for 15 months each to recruit 285 patients in total. Participants will be identified from speech and language therapy records and from voluntary support groups. People who have had aphasia for 4 months or more post stroke will be invited to take part. There will be no upper limit as people 10 years and more showed benefit from the therapy in the pilot study. In the pilot study, speech therapists together with a group of people with aphasia and their carers developed an accessible method to ensure consent from people with aphasia is fully informed. Those agreeing to participate will be randomly allocated to receiving the computer therapy, usual care, or puzzle books for regular purposeful activity. The intervention will consist of 6 months of therapy. Participants will be assessed by a speech and language therapist who will tailor the computer exercises to meet their needs. The software will be installed on the participant's own computer if they have one. If not, a lap top and software will be loaned for the trial period. They will be asked to manage their own practice with the computer for 20-30 minutes a day for 6 months. Volunteers or speech and language therapy assistants will be trained by the speech and language therapist, as piloted, to provide technical support and encouragement to the participant. The participants in the usual care group will continue to receive the usual local provision for people at their stage of recovery. This may include continued face to face speech therapy in some areas. For others, usual care will be going to support groups or having everyday conversations. The latter is the most likely form of usual care for those more than 12 months post stroke. A third group will be offered daily puzzles to complete and monthly telephone calls from a researcher. All groups will continue to access usual care in addition to any extra input offered by the study. Measurements will include: the change in the percentage of words named correctly; ratings of conversation ability; patient and carer perceptions of communication ability and quality of life. These will be made at recruitment, and after 6 months, 9 months and 12 months. The speech therapists carrying out the measurements will not know which group the participants are in. Data will be collected for an evaluation of whether this therapy is cost effective. The research team includes researchers who have substantial clinical experience as qualified speech and language therapists, members of a clinical trials research unit experienced in running large trials and a statistician and health economist who will analyse the information collected. The advisory group consists of people with aphasia and their carers. The team have worked together on the pilot study that informed this application. This research will enable NHS commissioners, patients and relatives to make informed decisions about using this model of computer treatment for people with persistent aphasia.

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;7.3 MANAGEMENT AND DECISION MAKING
Health categories: STROKE