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Abstract Background Ideally clinical trials should use some form of randomization for allocating participants to the treatment groups under trial. As an integral part of the process of assessing the effectiveness of these treatment groups, randomization performed well can reduce, if not eliminate, some forms of bias that can be evident in non-randomized trials. Given the vast set of possible randomization methods to choose from we demonstrate a method that incorporates many of the advantages of these other methods. Methods A step-by-step introduction of how to use the adaptive randomization algorithm for conducting a clinical trial is given. Results The implications, effects and capabilities of using the adaptive randomization algorithm are fully demonstrated and explained using simulated data and examples from actual trials. Conclusions This paper provides an introduction to a dynamic type of treatment allocation, which fulfills the CONSORT requirements of participants being randomly allocated whilst maintaining a level of control of the balances overall, within the stratification variables and within the strata simultaneously. Maintaining control of the imbalances within the groups is vital particularly if interim analyses are planned. Trial registration Current controlled trials ISRCTN17551624, ISRCTN37558856, ISRCTN97185214.

Abstract Background A strong consensus exists for a systematic approach to linguistic validation of patient reported outcome measures (PROMs) and discrete methods for assessing their psychometric properties. Despite the need for robust evidence of the appropriateness of measures, transition from linguistic to psychometric validation is poorly documented or evidenced. This paper demonstrates the importance of linking linguistic and psychometric testing through a purposeful stage which bridges the gap between translation and large-scale validation. Findings Evidence is drawn from a study to develop a Welsh language version of the Beck Depression Inventory-II (BDI-II) and investigate its psychometric properties. The BDI-II was translated into Welsh then administered to Welsh-speaking university students (n = 115) and patients with depression (n = 37) concurrent with the English BDI-II, and alongside other established depression and quality of life measures. A Welsh version of the BDI-II was produced that, on administration, showed conceptual equivalence with the original measure; high internal consistency reliability (Cronbach’s alpha = 0.90; 0.96); item homogeneity; adequate correlation with the English BDI-II (r = 0.96; 0.94) and additional measures; and a two-factor structure with one overriding dimension. Nevertheless, in the student sample, the Welsh version showed a significantly lower overall mean than the English (p = 0.002); and significant differences in six mean item scores. This prompted a review and refinement of the translated measure. Conclusions Exploring potential sources of bias in translated measures represents a critical step in the translation-validation process, which until now has been largely underutilised. This paper offers important findings that inform advanced methods of cross-cultural validation of PROMs.

Abstract Background There is a lack of high quality, child-centred and effective health information to support development of self-care practices and expertise in children with acute and long-term conditions. In type 1 diabetes, clinical guidelines indicate that high-quality, child-centred information underpins achievement of optimal glycaemic control with the aim of minimising acute readmissions and reducing the risk of complications in later life. This paper describes the development of a range of child-centred diabetes information resources and outlines the study design and protocol for a randomized controlled trial to evaluate the information resources in routine practice. The aim of the diabetes information intervention is to improve children and young people's quality of life by increasing self-efficacy in managing their type 1 diabetes. Methods/Design We used published evidence, undertook qualitative research and consulted with children, young people and key stakeholders to design and produce a range of child-centred, age-appropriate children's diabetes diaries, carbohydrate recording sheets, and assembled child-centred, age-appropriate diabetes information packs containing published information in a folder that can be personalized by children and young people with pens and stickers. Resources have been designed for children/young people 6-10; 11-15; and 16-18 years. To evaluate the information resources, we designed a pragmatic randomized controlled trial to assess the effectiveness, cost effectiveness, and implementation in routine practice of individually tailored, age-appropriate diabetes diaries and information packs for children and young people age 6-18years, compared with currently available standard practice. Children and young people will be stratified by gender, length of time since diagnosis (< 2years and > 2years) and age (6-10; 11-15; and 16-18 years). The following data will be collected at baseline, 3 and 6 months: PedsQL (generic, diabetes and parent versions), and EQ-5 D (parent and child); NHS resource use and process data (questionnaire and interview). Baseline and subsequent HbA1c measurements, blood glucose meter use, readings and insulin dose will be taken from routine test results and hand-held records when attending routine 3-4 monthly clinic visits. The primary outcome measure is diabetes self-efficacy and quality-of-life (Diabetes PedsQL). Secondary outcomes include: HbA1c, generic quality of life, routinely collected NHS/child-held data, costs, service use, acceptability and utility. Trial Registration ISRCTN17551624.

Abstract Background Quality of residential care for people with severe dementia is in urgent need of improvement. One reason for this may be the assumption that people with severe dementia are unaware of what is happening to them. However, there is converging evidence to suggest that global assumptions of unawareness are inappropriate. This trial platform study aims to assist care staff in perceiving and responding to subtle signs of awareness and thus enhance their practice. Methods/Design In Stage One, a measure of awareness in severe dementia will be developed. Two focus groups and an expert panel will contribute to item and scale development. In Stage Two observational data will be used to further develop the measure. Working in four care homes, we will recruit 40 individuals with severe dementia who have no, or very limited, verbal communication. Data on inter-rater reliability and frequency of all items and exploratory factor analysis will be used to identify items to be retained. Test-retest and inter-rater reliability for the new measure will be calculated. Correlations with scores for well-being and behaviour and with proxy ratings of quality of life will provide an indication of concurrent validity. In Stage Three the new measure will be used in a single blind cluster randomised trial. Eight care homes will participate, with 10 residents recruited in each giving a total sample of 80 people with severe dementia. Homes will be randomised to intervention or usual care conditions. In the intervention condition, staff will receive training in using the new measure and will undertake observations of designated residents. For residents with dementia, outcomes will be assessed in terms of change from baseline in scores for behaviour, well-being and quality of life. For care staff, outcomes will be assessed in terms of change from baseline in scores for attitudes, care practice, and well-being. Discussion The results will inform the design of a larger-scale trial intended to provide definitive evidence about the benefits of increasing the sensitivity of care staff to signs of awareness in residents with severe dementia. Trial Registration ISRCTN59507580 http://www.controlled-trials.com.

Abstract This correction reports changes in our protocol since its publication. These include changes to authorship and acknowledgements, together with improvements to study design and procedures, and correction of an internal inconsistency. The improvements relate to the exclusion criteria, assessments carried out at screening, and mode of data collection.

Abstract Background Clinical depression is common, debilitating and treatable; one in four people experience it during their lives. The majority of sufferers are treated in primary care and only half respond well to active treatment. Evidence suggests that folate may be a useful adjunct to antidepressant treatment: 1) patients with depression often have a functional folate deficiency; 2) the severity of such deficiency, indicated by elevated homocysteine, correlates with depression severity, 3) low folate is associated with poor antidepressant response, and 4) folate is required for the synthesis of neurotransmitters implicated in the pathogenesis and treatment of depression. Methods/Design The primary objective of this trial is to estimate the effect of folate augmentation in new or continuing treatment of depressive disorder in primary and secondary care. Secondary objectives are to evaluate the cost-effectiveness of folate augmentation of antidepressant treatment, investigate how the response to antidepressant treatment depends on genetic polymorphisms relevant to folate metabolism and antidepressant response, and explore whether baseline folate status can predict response to antidepressant treatment. Seven hundred and thirty patients will be recruited from North East Wales, North West Wales and Swansea. Patients with moderate to severe depression will be referred to the trial by their GP or Psychiatrist. If patients consent they will be assessed for eligibility and baseline measures will be undertaken. Blood samples will be taken to exclude patients with folate and B12 deficiency. Some of the blood taken will be used to measure homocysteine levels and for genetic analysis (with additional consent). Eligible participants will be randomised to receive 5 mg of folic acid or placebo. Patients with B12 deficiency or folate deficiency will be given appropriate treatment and will be monitored in the 'comprehensive cohort study'. Assessments will be at screening, randomisation and 3 subsequent follow-ups. Discussion If folic acid is shown to improve the efficacy of antidepressants, then it will provide a safe, simple and cheap way of improving the treatment of depression in primary and secondary care. Trial registration Current controlled trials ISRCTN37558856

Background: Very few interventional studies have directly examined the impact of treatment approaches on health-related quality of life (HRQL) in people with dementia. This is of particular importance in therapies to address behavioural symptoms, where HRQL is often severely affected.Methods: Analysis within the WHELD cluster randomised factorial study in 16 UK care homes examining the impact of person-centred care in combination with antipsychotic review, social interaction and exercise interventions. This study analysed impact on HRQL through the DEMQOL-Proxy.Results: Data on HRQL were available for 187 participants. People receiving antipsychotic review showed a significant worsening in two DEMQOL-Proxy domains (negative emotion: p = 0.02; appearance: p = 0.04). A best-case scenario analysis showed significant worsening for total DEMQOL-Proxy score. Social interaction intervention resulted in a significant benefit to HRQL (p = 0.04). There was no deterioration in HRQL in groups receiving both antipsychotic review and social interaction (p = 0.62).Conclusions: This demonstrates an important detrimental impact of discontinuation of antipsychotics in dementia on HRQL, highlighting the need for careful review of best practice guidelines regarding antipsychotic use and emphasising the importance of providing evidence-based non-pharmacological interventions in conjunction with antipsychotic review. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]