Pragmatic cluster randomised controlled trial of contextualised grammar teaching and small group teaching to improve the writing skills of 11 year old children

Introduction: We evaluated two interventions: a contextualised grammar teaching intervention – Grammar for Writing - to assess whether it improved 11 year old children’s writing skills; and a small group literacy intervention to assess whether or not this was effective. Design and method: We used a pragmatic cluster randomised trial with partial split plot design. Independent concealed randomisation was undertaken at the class level, and, within the intervention group, children were also individually randomised to receive the whole class intervention plus a small group intervention or to receive the intervention in a whole class setting only. The main outcomes were writing and reading assessed by the Progress in English 11 (Long Form) test (GL Assessment). Results: In 2013, 55 schools in England, each with two classes, were recruited and randomised. Within each school, the two classes were randomly allocated to receive either the intervention or the control condition. After randomisation, 2 schools withdrew, leaving 53 schools, 106 classes and 2510 pupils. We observed an effect size (ES) of 0.10 favouring the Grammar for Writing classes; however, this was not statistically significant (95% confidence interval (CI) -0.10 to 0.31). Pupils randomised to the small groups had an increased literacy score when compared with the control classes (ES = 0.24, 95% CI 0.00 to 0.49) and when compared with the intervention children taught in the whole class (ES = 0.21, 95% CI 0.04 to 0.38). Conclusion: There is little evidence that this form of contextualised grammar teaching had an effect on 11 year old children’s writing skills. There was some evidence of an effect for small group teaching

Randomised, controlled trial of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers : PRESSURE (pressure relieving support surfaces) trial

Objective To compare whether differences exist between alternating pressure overlays and alternating pressure mattresses in the development of new pressure ulcers, healing of existing pressure ulcers, and patient acceptability. Design Pragmatic, open, multicentre, randomised controlled trial. Setting 11 hospitals in six NHS trusts. Participants 1972 people admitted to hospital as acute or elective patients. Interventions Participants were randomised to an alternating pressure mattress (n = 982) of- an alternating pressure overlay (n = 990). Main outcome measures The proportion of participants developing a new pressure ulcer of grade 2 or worse; time to development of new pressure ulcers; proportions of participants developing a new ulcer within 30 days; healing of existing pressure ulcers; and patient acceptability Results Intention to treat analysis found no difference in the proportions of participants developing a new pressure ulcer of grade 2 or worse (10.7% overlay patients, 10.3% mattress patients; difference 0.4%, 95% confidence interval - 23% to 3.1%, P = 0.75). More overlay patients requested change owing to dissatisfaction (23.3%) than mattress patients (18.9%, P = 0.02). Conclusion No difference was found between alternating pressure mattresses and alternating pressure overlays in the proportion of people who develop a pressure ulcer

An evaluation of a personalised text message reminder compared to a standard text message on postal questionnaire response rates: an embedded randomised controlled trial

Abstract Background: Research outcome data is commonly collected using postal questionnaires; however, poor response can introduce bias and reduce statistical power. Text messaging is simple, cost-effective, and can be customised to the individual. Personalised, reminder text messages may improve response rates. Methods: A two-arm, parallel group ‘Study within a Trial’ (SWAT) was embedded within the Occupational Therapist Intervention Study (OTIS), a randomised controlled trial of a home assessment for falls prevention in older people. OTIS participants who provided a mobile phone number were randomly allocated (1:1) to receive either a personalised text message (Title, Surname, plus York Trials Unit (YTU) text) or the standard YTU text alone, prior to receiving their four-month post-randomisation follow-up postal questionnaire. The primary outcome measure was the proportion of participants who returned the questionnaire. Secondary outcomes were: time to response, completeness of response, requirement of a reminder letter, and cost-effectiveness. Binary data were compared using logistic regression and time to response by Cox Proportional Hazards regression. Results: A total of 403 participants were randomised: 201 to the personalised text and 202 to the standard text. Of the 283 participants included in the final analysis, 278 (98.2%) returned their questionnaire; 136 (97.8%) for the personalised text versus 142 (98.6%) for the standard text (adjusted odds ratio 0.64, 95% CI 0.10 to 3.88, p=0.63). The median time to response was nine days in both groups. In total, 271 (97.5%) participants returned a complete questionnaire; 133 (97.8%) in the personalised text versus 138 (97.2%) for the standard text. In total, 21 reminder letters were sent. The additional cost of personalised text messages was £0.04 per participant retained. Conclusions: Personalised texts were not superior to standard texts in any outcome assessed in our study. Further SWATs are needed to perform a meta-analysis and obtain more evidence. Registration: ISRCTN22202133; SWAT 35 Keywords: SWAT, Randomised Controlled Trial, personalised, SMS text, postal questionnaire, reminde

No difference found in time to publication by statistical significance of trial results: a methodological review

Objective: Time-lag from study completion to publication is a potential source of publication bias in randomised controlled trials. This study sought to update the evidence base by identifying the effect of the statistical significance of research findings on time to publication of trial results.Design: Literature searches were carried out in four general medical journals from June 2013 to June 2014 inclusive (BMJ, JAMA, the Lancet and the New England Journal of Medicine). Setting: Methodological review of four general medical journals. Participants: Original research articles presenting the primary analyses from phase 2, 3 and 4 parallel-group randomised controlled trials were included. Main outcome measures: Time from trial completion to publication.Results: The median time from trial completion to publication was 431 days (n ¼ 208, interquartile range 278–618). A multivariable adjusted Cox model found no statistically significant difference in time to publication for trials reporting positive or negative results (hazard ratio: 0.86, 95% CI 0.64 to 1.16, p ¼ 0.32). Conclusion: In contrast to previous studies, this review did not demonstrate the presence of time-lag bias in time to publication. This may be a result of these articles being published in four high-impact general medical journals that may be more inclined to publish rapidly, whatever the findings. Further research is needed to explore the presence of time-lag bias in lower quality studies and lower impact journals

What type of environmental assessment and modification prevents falls in community dwelling older people?

What you need to know • Evidence suggests that environmental interventions can prevent falls in older people at high risk of falls, but they have little or no benefit in people at low risk • Offer environmental assessment and modification led by an occupational therapist to people over 65 who have had a fall in the past year, use a mobility aid, need assistance with any activities of daily living, take psychoactive medications, or are concerned about falling • Environmental assessment and modification encompasses a comprehensive, validated functional assessment of the individual in their home environment, a joint problem solving approach, and follow-up as require

An embedded randomised controlled retention trial of personalised text messages compared to non-personalised text messages in an orthopaedic setting [version 1; peer review: 1 approved]

Background: Several studies have investigated whether personalising trial documentation can aid recruitment and retention. We did a ‘study within a trial’ (SWAT) evaluating the effectiveness of a personalised text message compared to a non-personalised text message, on the retention rate in a large orthopaedic trial. Methods: The SWAT was embedded in the Knee Replacement Bandaging Study (KReBS) trial. The primary outcome was the proportion of 12-month questionnaires returned. Secondary outcomes were the proportion of questionnaires completed and time to questionnaire return. Binary data were analysed using logistic regression and time to return using Cox proportional hazards regression. Odds ratios (OR) and hazard ratios (HR) are presented, with associated 95% confidence intervals (CI) and p-values. Results: In total, 1465 participants were included in the SWAT. In the personalised group, 644/723 (89.1%) of participants returned a questionnaire, compared to 654/742 (88.1%) in the non-personalised group. The absolute difference in return rate was 0.9% (95% CI: -2.3% to 4.2%; p=0.57). There was no evidence of a difference between the groups in the likelihood of returning a questionnaire (OR 1.09; 95% CI: 0.79 to 1.51; p=0.61), the likelihood of returning a complete questionnaire (OR 1.11; 95% CI: 0.82 to 1.51; p=0.50) nor in time to return (HR 1.05; 95% CI: 0.94 to 1.17; p=0.40). Conclusion: This SWAT adds to the growing evidence base for whether personalised text messages are effective. Registration: ISRCTN87127065 (20/02/2017); SWAT 35 (01/12/2015

Effectiveness of pre-operative anaemia screening and increased Tranexamic acid dose policies on outcomes following unilateral primary, elective total hip or knee replacement : a statistical analysis plan for an interrupted time series and regression discontinuity study

Perioperative blood transfusion is associated with poorer postoperative outcomes following hip and knee replacement surgery. Evidence for the effectiveness of some measures aimed at reducing blood transfusions in this setting are limited and often rely on weak pre-post study designs. Quasi-experimental study designs such as interrupted time series (ITS) and regression discontinuity design (RDD) address many of the weaknesses of the pre-post study design. In addition, a priori publication of statistical analysis plans for such studies increases their transparency and likely validity, as readers are able to distinguish between pre-planned and exploratory analyses. As such, this article, written prospective of any analysis, provides the statistical analysis plan for an ITS and RDD study based on a data set of 20,772 primary elective hip and knee replacement patients in a single English NHS Trust. The primary aim is to evaluate the impact of a preoperative anaemia optimisation service on perioperative blood transfusion (within 7 days of surgery) using both ITS and RDD methods. A secondary aim is to evaluate the impact of a policy of increased tranexamic acid dose given at the time of surgery, using ITS methods

Exploring Engagement with Authors of Randomised Controlled Trials to Develop Recommendations to Improve Allocation Concealment Implementation and Reporting

Background: Reviews have consistently shown that allocation concealment is frequently implemented and reported suboptimally in randomised controlled trials (RCTs). This research aims to pilot engaging with authors of RCTs to explore their knowledge and understanding of allocation concealment implementation and reporting to ascertain areas and mechanisms for their improvement. Methods: Authors that published RCTs in core clinical journals in one month in 2019 were identified. Authors were invited to complete questionnaires to elicit their views and experiences on the implementation and reporting quality focussing on allocation concealment. Methodological quality of allocation concealment was evaluated in this sample by assessing adherence to the Consolidated Standards of Reporting Trials (CONSORT). Results: Reporting was suboptimal, with only 57% of allocation concealment methods reported to be implemented which were judged as adequate, with 18% using sealed envelopes and more than 40% not adequately reporting allocation methods. When exploring allocation concealment, implementation and reporting questionnaires were found to elicit a low response rate amongst authors of RCTs. Discussion: Following analysis of the themes that emerged from the questionnaires, the main recommendations to improve reporting quality are: journals need to endorse, adhere and promote reporting guidelines, a methodologist could review methodological details of publications simultaneously to peer review, envelopes as a form of allocation concealment are poorly implemented and reported, so careful review of these is required, funders need to insist on more robust allocation concealment methods are employed if the RCT setting allows, and authors need to acknowledge their responsibility for transparent reporting of RCTs

Qualitative research to inform hypothesis testing for fidelity-based sub-group analysis in clinical trials : lessons learnt from the process evaluation of a multifaceted podiatry intervention for falls prevention

Background: Ensuring fidelity to complex interventions is a challenge when conducting pragmatic randomised controlled trials. We explore fidelity through a qualitative process evaluation, which was conducted alongside a pragmatic, multicentre, two-arm cohort randomised controlled trial: the REFORM (Reducing Falls with Orthoses and a Multifaceted podiatry intervention) trial. The paper aims, through a qualitative process evaluation, to explore some of the factors that may have affected the delivery of the REFORM intervention and highlight how project-specific fidelity can be assessed using a truly mixed-methods approach when informed by qualitative insights. Design: Semi-structured qualitative interviews carried out as part of a process evaluation. Interviews were analysed thematically. Setting: Seven NHS trusts in the UK and a University podiatry school in Ireland. Interviews were undertaken face-toface or over the telephone. Participants: Twenty-one REFORM trial participants and 14 podiatrists who delivered the REFORM intervention. Results: Factors affecting fidelity included: how similar the intervention was to routine practice; the challenges of delivering a multifaceted intervention to a heterogeneous older population; and practical issues with delivery such as time and training. Trial participants’ views of the intervention, whether falls prevention is a personal priority, their experience of being part of a trial and individual factors such as medical conditions may also have affected intervention fidelity. Conclusions: Our process evaluation highlighted factors that were perceived to have affected the fidelity of the REFORM intervention and in doing so demonstrates the importance of considering fidelity when designing and evaluating pragmatic trials. We propose a number of recommendations of how important project-specific insights from qualitative work can be incorporated into the design of fidelity measurement of future trials, which build on existing conceptual fidelity frameworks. In particular, we encourage adopting a mixed-methods approach whereby qualitative insights can be used to suggest ways to enhance quantitative data collection facilitating integration through hypothesis generation, hypothesis testing and seeking explanation for trial findings. This will provide a framework of enabling measures of fidelity to be incorporated into the understanding of trial results which has been relatively neglected by existing literature. Trial registration: ISRCTN Registry: ISRCTN68240461. Registered on 01/07/2011. Keywords: Process evaluation, Randomised controlled trials, Fidelity, Mixed methods, Falls, Elderly, Ageing, Qualitativ

The evidence base for emergency use authorizations for COVID-19 treatments : A rapid review

Background and Aims During the COVID-19 pandemic, US Food and Drug Administration (FDA) permitted emergency use authorizations (EUAs) for vaccines/treatments with promising data. Eight treatments were issued EUAs by May 31, 2021; one of these was approved (Remdesivir for certain populations) and two were revoked (chloroquine phosphate/hydroxychloroquine and bamlanivimab) by September 30, 2021. The aim of this study is to find out what evidence the EUAs were based on and how many studies were published while they remained active (up to September 30, 2021). Methods A review of published clinical studies for the 6 months before each EUA was issued, and the time after (until September 30, 2021, or until revoked). PubMed and the identified systematic reviews were the sources for identifying published literature. Results The number of clinical studies published pre-EUA varied from a single case study (for chloroquine phosphate/hydroxychloroquine) to numerous studies of multiple types (for convalescent plasma). Four treatments had a single randomized controlled trial (RCT) as evidence (bamlanivimab monotherapy, REGN-COV, bamlanivimab + etesevimab,sotrovimab) and two also had other study types (remdesivir and baricitinib). The number of clinical studies published post-EUA (for those active on September 30, 2021) was widely varied. Eighteen RCTs were published for Convalescent plasma, while Remdesivir had eight. Baricitinib, REGN-COV, and bamlanivimab + etesevimab all had one, but none were published for sotrovimab. Conclusion The number of trials for treatments with EUAs was limited in all cases before the EUA was issued, and in most cases for those with EUAs ongoing at the end of September 2021. The presence of EUAs may discourage participation in relevant clinical trials, which delays the widespread implementation of evidenced-based therapies. Large, robust RCTs should be completed, such as the RECOVERY trial in the United Kingdom, to quickly find the answers desperately required during a pandemic