A review of economic evaluations of health care for people at risk of psychosis and for first-episode psychosis.

BACKGROUND: Preventing psychotic disorders and effective treatment in first-episode psychosis are key priorities for the National Institute for Health and Care Excellence. This review assessed the evidence base for the cost-effectiveness of health and social care interventions for people at risk of psychosis and for first-episode psychosis. METHODS: Electronic searches were conducted using the PsycINFO, MEDLINE and Embase databases to identify relevant published full economic evaluations published before August 2020. Full-text English-language studies reporting a full economic evaluation of a health or social care intervention aiming to reduce or prevent symptoms in people at risk of psychosis or experiencing first-episode psychosis were included. Screening, data extraction, and critical appraisal were performed using pre-specified criteria and forms based on the NHS Economic Evaluation Database (EED) handbook and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist for economic evaluations. The protocol was registered on the PROSPERO database (CRD42018108226). Results were summarised qualitatively. RESULTS: Searching identified 1,628 citations (1,326 following the removal of duplications). After two stages of screening 14 studies met the inclusion criteria and were included in the review. Interventions were varied and included multidisciplinary care, antipsychotic medication, psychological therapy, and assertive outreach. Evidence was limited in the at-risk group with only four identified studies, though all interventions were found to be cost-effective with a high probability (> 80%). A more substantial evidence base was identified for first-episode psychosis (11 studies), with a focus on early intervention (7/11 studies) which again had positive conclusions though with greater uncertainty. CONCLUSIONS: Study findings generally concluded interventions were cost-effective. The evidence for the population who are at-risk of psychosis was limited, and though there were more studies for the population with first-episode psychosis, limitations of the evidence base (including generalisability and heterogeneity across the methods used) affect the certainty of conclusions.

Hospital admissions and place of death of residents of care homes receiving specialist healthcare services: A systematic review without meta-analysis.

AIM: To synthesize evidence on the ability of specialist care home support services to prevent hospital admission of older care home residents, including at end of life. DESIGN: Systematic review, without meta-analysis, with vote counting based on direction of effect. DATA SOURCES: Fourteen electronic databases were searched from January 2010 to January 2019. Reference lists of identified reviews, study protocols and included documents were scrutinized for further studies. REVIEW METHODS: Papers on the provision of specialist care home support that addressed older, long-term care home residents' physical health needs and provided comparative data on hospital admissions were included. Two reviewers undertook study selection and quality appraisal independently. Vote counting by direction of effect and binomial tests determined service effectiveness. RESULTS: Electronic searches identified 79 relevant references. Combined with 19 citations from an earlier review, this gave 98 individual references relating to 92 studies. Most were from the UK (22), USA (22) and Australia (19). Twenty studies were randomized controlled trials and six clinical controlled trials. The review suggested interventions addressing residents' general health needs (p < .001), assessment and management services (p < .0001) and non-training initiatives involving medical staff (p < .0001) can reduce hospital admissions, while there was also promising evidence for services targeting residents at imminent risk of hospital entry or post-hospital discharge and training-only initiatives. End-of-life care services may enable residents to remain in the home at end of life (p < .001), but the high number of weak-rated studies undermined confidence in this result. CONCLUSION: This review suggests specialist care home support services can reduce hospital admissions. More robust studies of services for residents at end of life are urgently needed. IMPACT: The review addressed the policy imperative to reduce the avoidable hospital admission of older care home residents and provides important evidence to inform service design. The findings are of relevance to commissioners, providers and residents.

Protocol for the economic evaluation of metacognitive therapy for cardiac rehabilitation participants with symptoms of anxiety and/or depression.

INTRODUCTION: Cardiac rehabilitation (CR) is offered to reduce the risk of further cardiac events and to improve patients' health and quality of life following a cardiac event. Psychological care is a common component of CR as symptoms of depression and/or anxiety are more prevalent in this population, however evidence for the cost-effectiveness of current interventions is limited. Metacognitive therapy (MCT), is a recent treatment development that is effective in treating anxiety and depression in mental health settings and is being evaluated in CR patients. This protocol describes the planned approach to the economic evaluation of MCT for CR patients. METHODS AND ANALYSIS: The economic evaluation work will consist of a within-trial analysis and an economic model. The PATHWAY Group MCT study has been prospectively designed to collect comprehensive self-reported resource use and health outcome data, including the EQ-5D, within a randomised controlled trial study design (UK Clinical Trials Gateway). A within-trial economic evaluation and economic model will compare the cost-effectiveness of MCT plus usual care (UC) to UC, from a health and social care perspective in the UK. The within-trial analysis will use intention-to-treat and estimate total costs and quality-adjusted life-years (QALYs) for the trial follow-up. Single imputation will be used to impute missing baseline variables. Multiple imputation will be used to impute values missing at follow-up. Items of resource use will be multiplied by published national healthcare costs. Regression analysis will be used to estimate net costs and net QALYs and these estimates will be bootstrapped to generate 10 000 net pairs of costs and QALYs to inform the probability of cost-effectiveness. A decision analytical economic model will be developed to synthesise trial data with the published literature over a longer time frame. Sensitivity analysis will explore uncertainty. Guidance of the methods for economic models will be followed and dissemination will adhere to reporting guidelines. ETHICS AND DISSEMINATION: The economic evaluation includes a within-trial analysis. The trial which included the collection of this data was reviewed and approved by Ethics. Ethics approval was obtained by the Preston Research Ethics Committee (project ID 156862). The modelling analysis is not applicable for Ethics as it will use data from the trial (secondary analysis) and the published literature. Results of the main trial and economic evaluation will be published in the peer-reviewed National Institute for Health Research (NIHR) journals library (Programme Grants for Applied Research), submitted to a peer-reviewed journal and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: ISRCTN74643496; Pre-results.

Cost-Effectiveness Evaluations of Psychological Therapies for Schizophrenia and Bipolar Disorder: A Systematic Review.

OBJECTIVES: This review aims to assess the cost-effectiveness of psychological interventions for schizophrenia/bipolar disorder (BD), to determine the robustness of current evidence and identify gaps in the available evidence. METHODS: Electronic searches (PsycINFO, MEDLINE, Embase) identified economic evaluations relating incremental cost to outcomes in the form of an incremental cost-effectiveness ratio published in English since 2000. Searches were concluded in November 2018. Inclusion criteria were: adults with schizophrenia/BD; any psychological/psychosocial intervention (e.g., psychological therapy and integrated/collaborative care); probability of cost-effectiveness at explicitly defined thresholds reported. Comparators could be routine practice, no intervention, or alternative psychological therapies. Screening, data extraction, and critical appraisal were performed using pre-specified criteria and forms. Results were summarized qualitatively. The protocol was registered on the PROSPERO database (CRD42017056579). RESULTS: Of 3,864 studies identified, 12 met the criteria for data extraction. All were integrated clinical and economic randomized controlled trials. The most common intervention was cognitive behavioral therapy (CBT, 6/12 studies). The most common measure of health benefit was the quality-adjusted life-year (6/12). Follow-up ranged from 6 months to 5 years. Interventions were found to be cost-effective in most studies (9/12): the probability of cost-effectiveness ranged from 35-99.5 percent. All studies had limitations and demonstrated uncertainty (particularly related to incremental costs). CONCLUSIONS: Most studies concluded psychological interventions for schizophrenia/BD are cost-effective, including CBT, although there was notable uncertainty. Heterogeneity across studies makes it difficult to reach strong conclusions. There is a particular need for more evidence in the population with BD and for longer-term evidence across both populations.

Cognitive-behavioural therapy for clozapine-resistant schizophrenia: the FOCUS RCT.

BACKGROUND: Clozapine (clozaril, Mylan Products Ltd) is a first-choice treatment for people with schizophrenia who have a poor response to standard antipsychotic medication. However, a significant number of patients who trial clozapine have an inadequate response and experience persistent symptoms, called clozapine-resistant schizophrenia (CRS). There is little evidence regarding the clinical effectiveness of pharmacological or psychological interventions for this population. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of cognitive-behavioural therapy (CBT) for people with CRS and to identify factors predicting outcome. DESIGN: The Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial was a parallel-group, randomised, outcome-blinded evaluation trial. Randomisation was undertaken using permuted blocks of random size via a web-based platform. Data were analysed on an intention-to-treat (ITT) basis, using random-effects regression adjusted for site, age, sex and baseline symptoms. Cost-effectiveness analyses were carried out to determine whether or not CBT was associated with a greater number of quality-adjusted life-years (QALYs) and higher costs than treatment as usual (TAU). SETTING: Secondary care mental health services in five cities in the UK. PARTICIPANTS: People with CRS aged ≥ 16 years, with an International Classification of Diseases, Tenth Revision (ICD-10) schizophrenia spectrum diagnoses and who are experiencing psychotic symptoms. INTERVENTIONS: Individual CBT included up to 30 hours of therapy delivered over 9 months. The comparator was TAU, which included care co-ordination from secondary care mental health services. MAIN OUTCOME MEASURES: The primary outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 21 months and the primary secondary outcome was PANSS total score at the end of treatment (9 months post randomisation). The health benefit measure for the economic evaluation was the QALY, estimated from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), health status measure. Service use was measured to estimate costs. RESULTS: Participants were allocated to CBT (n = 242) or TAU (n = 245). There was no significant difference between groups on the prespecified primary outcome [PANSS total score at 21 months was 0.89 points lower in the CBT arm than in the TAU arm, 95% confidence interval (CI) -3.32 to 1.55 points; p = 0.475], although PANSS total score at the end of treatment (9 months) was significantly lower in the CBT arm (-2.40 points, 95% CI -4.79 to -0.02 points; p = 0.049). CBT was associated with a net cost of £5378 (95% CI -£13,010 to £23,766) and a net QALY gain of 0.052 (95% CI 0.003 to 0.103 QALYs) compared with TAU. The cost-effectiveness acceptability analysis indicated a low likelihood that CBT was cost-effective, in the primary and sensitivity analyses (probability < 50%). In the CBT arm, 107 participants reported at least one adverse event (AE), whereas 104 participants in the TAU arm reported at least one AE (odds ratio 1.09, 95% CI 0.81 to 1.46; p = 0.58). CONCLUSIONS: Cognitive-behavioural therapy for CRS was not superior to TAU on the primary outcome of total PANSS symptoms at 21 months, but was superior on total PANSS symptoms at 9 months (end of treatment). CBT was not found to be cost-effective in comparison with TAU. There was no suggestion that the addition of CBT to TAU caused adverse effects. Future work could investigate whether or not specific therapeutic techniques of CBT have value for some CRS individuals, how to identify those who may benefit and how to ensure that effects on symptoms can be sustained. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99672552. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 7. See the NIHR Journals Library website for further project information.

Hospital admissions and place of death of residents of care homes receiving specialist healthcare services: Protocol for a systematic review.

AIM: To synthesize the evidence relating to the ability of specialist care home support services to prevent the hospital admission of older care home residents, including hospital admission at the end-of-life. DESIGN: Systematic review and narrative synthesis. METHODS: Ten electronic databases will be searched from 2010 - 31 December 2018 using predetermined search terms. All studies of specialist healthcare services to meet care home residents' physical healthcare needs which provide outcome data on hospital admission or place of death compared with usual care will be included. Two reviewers will independently assess studies' eligibility and methodological quality using the Effective Public Health Practice Project Quality Assessment Tool. Data will be extracted by one reviewer and checked by a second according to predetermined categories. Data will be synthesized in evidence tables and narrative. Funder: National Institute for Health Research School for Social Care Research, November 2016. DISCUSSION: Care of older people in care home settings is a key aspect of nursing nationally and internationally. This review will increase understanding of the extent to which different models of specialist healthcare support for care homes are associated with key resident outcomes. IMPACT: Standard healthcare support for care home residents is often inadequate, resulting in avoidable hospital admissions and lack of resident choice as to place of death. Although a range of specialist healthcare services are emerging, little is known about their relative effectiveness. This paper marshalls evidence of relevance to commissioners investing in healthcare provision to care homes to meet NHS targets.

Reconfiguring in-patient services for adults with mental health problems: changing the balance of care.

BACKGROUND: Research suggests that a significant minority of hospital in-patients could be more appropriately supported in the community if enhanced services were available. However, little is known about these individuals or the services they require. AIMS: To identify which individuals require what services, at what cost. METHOD: A 'balance of care' (BoC) study was undertaken in northern England. Drawing on routine electronic data about 315 admissions categorised into patient groups, frontline practitioners identified patients whose needs could be met in alternative settings and specified the services they required, using a modified nominal group approach. Costing employed a public-sector approach. RESULTS: Community care was deemed appropriate for approximately a quarter of admissions including people with mild-moderate depression, an eating disorder or personality disorder, and some people with schizophrenia. Proposed community alternatives drew heavily on carer support services, community mental health teams and consultants, and there was widespread consensus on the need to increase out-of-hours community services. The costs of the proposed community care were relatively modest compared with hospital admission. On average social care costs increased by approximately £60 per week, but total costs fell by £1626 per week. CONCLUSIONS: The findings raise strategic issues for both national policymakers and local service planners. Patients who could be managed at home can be characterised by diagnosis. Although potential financial savings were identified, the reported cost differences do not directly equate to cost savings. It is not clear whether in-patient beds could be reduced. However, existing beds could be more efficiently used. DECLARATION OF INTEREST: None.

Cost-effectiveness of cardiac rehabilitation: a systematic review.

Patients may be offered cardiac rehabilitation (CR), a supervised programme often including exercises, education and psychological care, following a cardiac event, with the aim of reducing morbidity and mortality. Cost-constrained healthcare systems require information about the best use of budget and resources to maximise patient benefit. We aimed to systematically review and critically appraise economic studies of CR and its components. In January 2016, validated electronic searches of the National Health Service Economic Evaluation Database (NHS EED), Health Technology Assessment, PsycINFO, MEDLINE and Embase databases were run to identify full economic evaluations published since 2001. Two levels of screening were used and explicit inclusion criteria were applied. Prespecified data extraction and critical appraisal were performed using the NHS EED handbook and Drummond checklist. The majority of studies concluded that CR was cost-effective versus no CR (incremental cost-effectiveness ratios (ICERs) ranged from $1065 to $71 755 per quality-adjusted life-year (QALY)). Evidence for specific interventions within CR was varied; psychological intervention ranged from dominant (cost saving and more effective) to $226 128 per QALY, telehealth ranged from dominant to $588 734 per QALY and while exercise was cost-effective across all relevant studies, results were subject to uncertainty. Key drivers of cost-effectiveness were risk of subsequent events and hospitalisation, hospitalisation and intervention costs, and utilities. This systematic review of studies evaluates the cost-effectiveness of CR in the modern era, providing a fresh evidence base for policy-makers. Evidence suggests that CR is cost-effective, especially with exercise as a component. However, research is needed to determine the most cost-effective design of CR.

A systematic review of stroke recognition instruments in hospital and prehospital settings.

BACKGROUND: We undertook a systematic review of all published stroke identification instruments to describe their performance characteristics when used prospectively in any clinical setting. METHODS: A search strategy was applied to Medline and Embase for material published prior to 10 August 2015. Two authors independently screened titles, and abstracts as necessary. Data including clinical setting, reported sensitivity, specificity, positive predictive value, negative predictive value were extracted independently by two reviewers. RESULTS: 5622 references were screened by title and or abstract. 18 papers and 3 conference abstracts were included after full text review. 7 instruments were identified; Face Arm Speech Test (FAST), Recognition of Stroke in the Emergency Room (ROSIER), Los Angeles Prehospital Stroke Screen (LAPSS), Melbourne Ambulance Stroke Scale (MASS), Ontario Prehospital Stroke Screening tool (OPSS), Medic Prehospital Assessment for Code Stroke (MedPACS) and Cincinnati Prehospital Stroke Scale (CPSS). Cohorts varied between 50 and 1225 individuals, with 17.5% to 92% subsequently receiving a stroke diagnosis. Sensitivity and specificity for the same instrument varied across clinical settings. Studies varied in terms of quality, scoring 13-31/36 points using modified Standards for the Reporting of Diagnostic accuracy studies checklist. There was considerable variation in the detail reported about patient demographics, characteristics of false-negative patients and service context. Prevalence of instrument detectable stroke varied between cohorts and over time. CPSS and the similar FAST test generally report the highest level of sensitivity, with more complex instruments such as LAPSS reporting higher specificity at the cost of lower detection rates. CONCLUSIONS: Available data do not allow a strong recommendation to be made about the superiority of a stroke recognition instrument. Choice of instrument depends on intended purpose, and the consequences of a false-negative or false-positive result.

What Difference Does Patient and Public Involvement Make and What Are Its Pathways to Impact? Qualitative Study of Patients and Researchers from a Cohort of Randomised Clinical Trials.

BACKGROUND: Patient and public involvement (PPI) is advocated in clinical trials yet evidence on how to optimise its impact is limited. We explored researchers' and PPI contributors' accounts of the impact of PPI within trials and factors likely to influence its impact. METHODS: Semi-structured qualitative interviews with researchers and PPI contributors accessed through a cohort of randomised clinical trials. Analysis of transcripts of audio-recorded interviews was informed by the principles of the constant comparative method, elements of content analysis and informant triangulation. RESULTS: We interviewed 21 chief investigators, 10 trial managers and 17 PPI contributors from 28 trials. The accounts of informants within the same trials were largely in agreement. Over half the informants indicted PPI had made a difference within a trial, through contributions that influenced either an aspect of a trial, or how researchers thought about a trial. According to informants, the opportunity for PPI to make a difference was influenced by two main factors: whether chief investigators had goals and plans for PPI and the quality of the relationship between the research team and the PPI contributors. Early involvement of PPI contributors and including them in responsive (e.g. advisory groups) and managerial (e.g. trial management groups) roles were more likely to achieve impact compared to late involvement and oversight roles (e.g. trial steering committees). CONCLUSION: Those seeking to enhance PPI in trials should develop goals for PPI at an early stage that fits the needs of the trial, plan PPI implementation in accordance with these goals, invest in developing good relationships between PPI contributors and researchers, and favour responsive and managerial roles for contributors in preference to oversight-only roles. These features could be used by research funders in judging PPI in trial grant applications and to inform policies to optimise PPI within trials.

A little more conversation please? Qualitative study of researchers' and patients' interview accounts of training for patient and public involvement in clinical trials.

BACKGROUND: Training in patient and public involvement (PPI) is recommended, yet little is known about what training is needed. We explored researchers' and PPI contributors' accounts of PPI activity and training to inform the design of PPI training for both parties. METHODS: We used semi-structured qualitative interviews with researchers (chief investigators and trial managers) and PPI contributors, accessed through a cohort of clinical trials, which had been funded between 2006 and 2010. An analysis of transcripts of audio-recorded interviews drew on the constant comparative method. RESULTS: We interviewed 31 researchers and 17 PPI contributors from 28 trials. Most researchers could see some value in PPI training for researchers, although just under half had received such training themselves, and some had concerns about the purpose and evidence base for PPI training. PPI contributors were evenly split in their perceptions of whether researchers needed training in PPI. Few PPI contributors had themselves received training for their roles. Many informants across all groups felt that training PPI contributors was unnecessary because they already possessed the skills needed. Informants were also concerned that training would professionalise PPI contributors, limiting their ability to provide an authentic patient perspective. However, informants welcomed informal induction 'conversations' to help contributors understand their roles and support them in voicing their opinions. Informants believed that PPI contributors should be confident, motivated, intelligent, focussed on helping others and have relevant experience. Researchers looked for these qualities when selecting contributors, and spoke of how finding 'the right' contributor was more important than accessing 'the right' training. CONCLUSIONS: While informants were broadly receptive to PPI training for researchers, they expressed considerable reluctance to training PPI contributors. Providers of training will need to address these reservations. Our findings point to the importance of reconsidering how training is conceptualised, designed and promoted and of providing flexible, learning opportunities in ways that flow from researchers' and contributors' needs and preferences. We also identify some areas of training content and the need for further consideration to be given to the selection of PPI contributors and models for implementing PPI to ensure clinical trials benefit from a diversity of patient perspectives.

An external pilot study to test the feasibility of a randomised controlled trial comparing eye muscle surgery against active monitoring for childhood intermittent exotropia [X(T)].

INTRODUCTION: The evidence base for the treatment of strabismus (squint) is poor. Our main aim is to improve this evidence base for the treatment of a common type of childhood squint {intermittent exotropia, [X(T)]}. We conducted an external pilot study in order to inform the design and conduct of a future full randomised controlled trial (RCT). METHODS: Children of between 6 months and 16 years with a recent diagnosis of X(T) were eligible for recruitment. Participants were recruited from secondary care at the ophthalmology departments at four UK NHS foundation trusts. Participants were randomised to either active monitoring or surgery. This report describes the findings of the Pilot Rehearsal Trial and Qualitative Study, and assesses the success against the objectives proposed. RECRUITMENT AND RETENTION: The experience gained during the Pilot Rehearsal Trial demonstrates the ability to recruit and retain sites that are willing to randomise children to both trial arms, and for parents to agree to randomisation of their children to such a study. One child declined the group allocation. A total of 231 children were screened (expected 240), of whom 138 (60%) were eligible (expected 228: 95%) and 49 (35% of eligible) children were recruited (expected 144: 63% of eligible). Strategies that improved recruitment over the course of the trial are discussed, together with the reasons why fewer children were eligible for recruitment than initially anticipated. Attrition was low. Outcome data were obtained for 47 of 49 randomised children. TRIAL PROCESSES AND DATA COLLECTION: The Trial Management processes proved effective. There were high levels of completion on all of the data collection forms. However, the feedback from the treatment orthoptists revealed that some modifications should be made to the length and frequency of the health service assessment and travel assessment questionnaires, thus reducing the burden on participants in the main trial. Modifications to the wording of the questions also need to be made. MONITORING OF BIAS: Children who recruited to the trial were older and had more severe strabismus than those children eligible but declining participation. Strategies to account for this in a full trial are proposed. REASONS FOR PARTICIPATION OR DECLINING STUDY: These were identified using qualitative interviews. The principal reasons for declining entry into the study were strong preferences for and against surgical treatment. HARMS: There were no serious unexpected adverse events. Two children had overcorrection of their X(T) with reduction in binocular vision following surgery, which is in line with previous studies. No children in the active monitoring arm developed a constant strabismus although two showed some reduction in control. CONCLUSIONS: The SamExo study has demonstrated that it is possible to recruit and retain participants to a randomised trial of surgery compared with active monitoring for X(T). For longer-term full RCTs, in order to maximise the generalisability of future studies, consideration needs to be given to planning more time and clinic appointments to assess eligibility and to allow consideration of participation; the greater use of research nurses for recruitment; and accommodating the strong preferences of some parents both for and against surgical intervention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN44114892. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 39. See the NIHR Journals Library website for further project information.

Surrendering control, or nothing to lose: Parents' preferences about participation in a randomised trial of childhood strabismus surgery.

BACKGROUND: Intermittent exotropia is the most common form of divergent strabismus (squint) in children. Evidence regarding its optimum management is limited. A pilot randomised controlled trial has recently been completed (Surgery versus Active Monitoring in Intermittent Exotropia trial) to determine the feasibility of a full randomised controlled trial. PURPOSE: To identify drivers for and barriers against parents' participation in Surgery versus Active Monitoring in Intermittent Exotropia and to seek their views on information received, the need for randomisation, and enhancing acceptability. METHODS: Multiple method qualitative study using semi-structured telephone interviews to explore parents' motivations and trial screening logs to provide an indication of common barriers. Exploratory thematic analysis identified key themes. RESULTS: A total of 48 interviews were conducted (14 participants; 34 non-participants). Barriers included no desire for surgery/preference to 'wait and see', wanting surgery immediately, feeling uncomfortable about 'surrendering control' over decision-making/being managed 'at random', lack of confidence in the effectiveness of surgery, believing the risks outweighed the benefits, and lack of trust. Drivers included desiring surgery, 'nothing to lose', benefits offsetting the risks, and being in a trial would result in better care. Some also mentioned 'doing their bit' for research. Suggestions for enhancing acceptability included allowing choice of treatment group, giving more time for decision-making, expanding on information given, and improving communication. Many felt the necessity of randomisation was adequately explained, but there was some indication that it was misunderstood. Information extracted from the screening logs of 80/89 eligible non-participants indicated the most prevalent barrier was not wanting surgery/preferring to observe (56%), followed by desiring surgery straightaway (15%). Opposition to randomisation/wanting to retain control was recorded in 9% of cases as was the belief that the child's squint was not severe enough to warrant surgery. LIMITATIONS: Interviews were not audio-recorded. Not all who consented to interview could be contacted, although the response/contact rate was good (48/62). A few parents did not provide reasons for refusing the trial. CONCLUSION: Opposition to surgery and concerns about surrendering control were common obstacles to participation, whereas parents keen for their child to undergo the operation but happy to defer tended to embrace a 'nothing to lose' attitude. Many non-participants would have consented if allowed to choose group, although most of these would have chosen observation. While most parents felt happy with information given and that randomisation was adequately explained, it is of concern that there may be some misunderstanding, which should be addressed in any trial. These findings will inform future trials in childhood exotropia, for example, consideration of preference arms and improving communication. Lessons learnt from the Surgery versus Active Monitoring in Intermittent Exotropia trial could prove valuable to paediatric and surgical trials generally.

From plans to actions in patient and public involvement: qualitative study of documented plans and the accounts of researchers and patients sampled from a cohort of clinical trials.

UNLABELLED: : Patient and public involvement (PPI) in research is increasingly required, although evidence to inform its implementation is limited. OBJECTIVE: Inform the evidence base by describing how plans for PPI were implemented within clinical trials and identifying the challenges and lessons learnt by research teams. METHODS: We compared PPI plans extracted from clinical trial grant applications (funded by the National Institute for Health Research Health Technology Assessment Programme between 2006 and 2010) with researchers' and PPI contributors' interview accounts of PPI implementation. Analysis of PPI plans and transcribed qualitative interviews drew on the Framework technique. RESULTS: Of 28 trials, 25 documented plans for PPI in funding applications and half described implementing PPI before applying for funding. Plans varied from minimal to extensive, although almost all anticipated multiple modes of PPI. Interview accounts indicated that PPI plans had been fully implemented in 20/25 trials and even expanded in some. Nevertheless, some researchers described PPI within their trials as tokenistic. Researchers and contributors noted that late or minimal PPI engagement diminished its value. Both groups perceived uncertainty about roles in relation to PPI, and noted contributors' lack of confidence and difficulties attending meetings. PPI contributors experienced problems in interacting with researchers and understanding technical language. Researchers reported difficulties finding 'the right' PPI contributors, and advised caution when involving investigators' current patients. CONCLUSIONS: Engaging PPI contributors early and ensuring ongoing clarity about their activities, roles and goals, is crucial to PPI's success. Funders, reviewers and regulators should recognise the value of preapplication PPI and allocate further resources to it. They should also consider whether PPI plans in grant applications match a trial's distinct needs. Monitoring and reporting PPI before, during and after trials will help the research community to optimise PPI, although the need for ongoing flexibility in implementing PPI should also be recognised.

The PedsQL™ as a measure of parent-rated quality of life in healthy UK toddlers: psychometric properties and cross-cultural comparisons.

The Pediatric Quality of Life Inventory (PedsQL(TM)) is a widely-used generic measure of health-related quality of life (HRQOL) in children aged ≥ 2 years. In the UK, mean scores are known for healthy children aged ≥ 5 years, but unknown for toddlers. This paper reports the psychometric properties of parent-rated PedsQL(TM) scores in healthy UK toddlers and compares scores with a healthy USA sample. Two-hundred and fifty-six parents of healthy 2-4-year-olds (recruited from UK Children's Centres/nurseries, University staff/volunteers, and a national parent forum) completed the toddler version of the PedsQL(TM). Internal consistency was good (≥ 0.70) for all except Nursery Functioning. There were ceiling effects but missing response rates were minimal. Mean scores were: Total score 87.8; Physical Health 92.6; Emotional Functioning 76.0; Social Functioning 89.9; Nursery Functioning 92.3; and Psychosocial Summary 84.6. UK parents rated higher on Physical and Nursery Functioning (p < 0.001), but worse than their US counterparts on Emotional Functioning (p < 0.001) and Psychosocial Summary (p = 0.004). In conclusion, the toddler version of the PedsQL(TM) performed well in a UK sample, apart from the Nursery Functioning scale. Further evidence is needed to ascertain its construct and discriminant validity in the UK. Differences between the UK and USA samples highlight the importance of cross-cultural variations.

Surgery versus Active Monitoring in Intermittent Exotropia (SamExo): study protocol for a pilot randomised controlled trial.

BACKGROUND: Childhood intermittent exotropia [X(T)] is a type of strabismus (squint) in which one eye deviates outward at times, usually when the child is tired. It may progress to a permanent squint, loss of stereovision and/or amblyopia (reduced vision). Treatment options for X(T) include eye patches, glasses, surgery and active monitoring. There is no consensus regarding how this condition should be managed, and even when surgery is the preferred option clinicians disagree as to the optimal timing. Reports on the natural history of X(T) are limited, and there is no randomised controlled trial (RCT) evidence on the effectiveness or efficiency of surgery compared with active monitoring. The SamExo (Surgery versus Active Monitoring in Intermittent Exotropia) pilot study has been designed to test the feasibility of such a trial in the UK. DESIGN: an external pilot patient randomised controlled trial. SETTING: four UK secondary ophthalmology care facilities at Newcastle NHS Hospitals Foundation Trust, Sunderland Eye Infirmary, Moorfields Eye Hospital and York NHS Trust. PARTICIPANTS: children aged between 6 months and 16 years referred with suspected and subsequently diagnosed X(T). Recruitment target is a total of 144 children over a 9-month period, with 120 retained by 9-month outcome visit.Randomisation: permuted blocks stratified by collaborating centre, age and severity of X(T). INTERVENTIONS: initial clinical assessment; randomisation (eye muscle surgery or active monitoring); 3-, 6- and 9-month (primary outcome) clinical assessments; participant/proxy completed questionnaire covering time and travel costs, health services use and quality of life (Intermittent Exotropia Questionnaire); qualitative interviews with parents to establish reasons for agreeing or declining participation in the pilot trial. OUTCOMES: recruitment and retention rates; nature and extent of participation bias; nature and extent of biases arising from crossover or loss to follow-up; reasons for agreeing/declining participation; variability of cure rates (to inform power calculations for a definitive RCT); completion rates of outcome measures. DISCUSSION: The SamExo pilot trial will provide important pointers regarding the feasibility of a full RCT of immediate surgery versus deferred surgery/active monitoring. The results of this pilot, including differences in cure rates, will inform the design of a definitive RCT. TRIAL REGISTRATION: ISRCTN44114892.

Surgical intervention in childhood intermittent exotropia: current practice and clinical outcomes from an observational cohort study.

PURPOSE: To describe surgical outcomes in intermittent exotropia (X(T)), and to relate these to preoperative and surgical characteristics. METHODS: 87 children (aged <11 years) underwent surgery in 18 UK centres; review data (mean 21 months post-surgery) were available for 72. The primary outcome measure was motor/sensory outcome (angle and stereoacuity). The secondary outcome measure was satisfactory control assessed by Newcastle Control Score (NCS). RESULTS: 35% of patients had excellent, 28% had fair and 37% had poor primary outcome. Preoperative and surgical characteristics did not influence primary outcome. Satisfactory control was achieved in 65% of patients, while X(T) remained/recurred in 20%. Persistent over-correction occurred in 15% of children. There was no relationship between over-correction and preoperative characteristics or surgical dose/type. Median angle improved by 12 prism dioptres (PD) at near and 19 PD at distance (p<0.001). Median NCS improved by 5 (p<0.001). 40% of those initially over-corrected remained so by last postoperative assessment; no relationship was found between an initial over-correction and good outcome. CONCLUSIONS: Whilst excellent motor/sensory outcome was achieved in one-third and satisfactory control in two-thirds of patients, the 37% poor outcome and 15% persistent over-correction rate is of concern. Surgical dose was similar in those under- and over-corrected, suggesting that over-corrections cannot be avoided merely by getting the dosage right: a randomised controlled trial (RCT) would shed light on this issue. Initial over-correction did not improve the chance of a good outcome, supporting the growing literature on this topic and further highlighting the need for randomised controlled trials of X(T) surgery.

The improving outcomes in intermittent exotropia study: outcomes at 2 years after diagnosis in an observational cohort.

BACKGROUND: The purpose of this study was to investigate current patterns of management and outcomes of intermittent distance exotropia [X(T)] in the UK. METHODS: This was an observational cohort study which recruited 460 children aged < 12 years with previously untreated X(T). Eligible subjects were enrolled from 26 UK hospital ophthalmology clinics between May 2005 and December 2006. Over a 2-year period of follow-up, clinical data were prospectively recorded at standard intervals from enrolment. Data collected included angle, near stereoacuity, visual acuity, control of X(T) measured with the Newcastle Control Score (NCS), and treatment. The main outcome measures were change in clinical outcomes (angle, stereoacuity, visual acuity and NCS) in treated and untreated X(T), 2 years from enrolment (or, where applicable, 6 months after surgery). Change over time was tested using the chi-square test for categorical, Wilcoxon test for non-parametric and paired-samples t-test for parametric data. RESULTS: At follow-up, data were available for 371 children (81% of the original cohort). Of these: 53% (195) had no treatment; 17% (63) had treatment for reduced visual acuity only (pure refractive error and amblyopia); 13% (50) had non surgical treatment for control (spectacle lenses, occlusion, prisms, exercises) and 17% (63) had surgery. Only 0.5% (2/371) children developed constant exotropia. The surgically treated group was the only group with clinically significant improvements in angle or NCS. However, 8% (5) of those treated surgically required second procedures for overcorrection within 6 months of the initial procedure and at 6-month follow-up 21% (13) were overcorrected. CONCLUSIONS: Many children in the UK with X(T) receive active monitoring only. Deterioration to constant exotropia, with or without treatment, is rare. Surgery appears effective in improving angle of X(T) and NCS, but rates of overcorrection are high.