Statistical analysis plan for the Ankle Injury Rehabilitation (AIR) Trial

Statistical Analysis Plan (SAP) for the Ankle Injury Rehabilitation (AIR) Trial AIR is a A multi-centre randomised controlled trial to assess the difference between plaster cast and functional bracing in the management of ankle fractures. This SAP describes the detailed statistical analyses for the AIR study and was agreed by the DMC prior to analyses taking plac

The effects of a UK review of breast cancer screening on uptake : an observational before/after study

Objectives: To measure whether uptake of breast cancer screening was affected by the publication of the Marmot Review and associated press coverage. Setting: Eight NHS breast screening centres in the West Midlands of the UK. Methods: Uptake of breast cancer screening invitations was compared in the week before and after the Marmot review publication. All 12,023 women invited for screening between 23 October 2012 and 5 November 2012 were included. A mixed effects model of the predictors of screening uptake (on date invited, or within 21 days) was created. Predictors considered for inclusion were whether the allocated screening appointment was before or after publication of the review, population factors (age, index of multiple deprivation income domain by quintile, previous attendance), and interaction terms. Results: Uptake decreased after publication of the review from 65% to 62% (OR = 0.87 95%CI = 0.80–0.94), but a similar decrease was seen for the same dates on the previous year (OR = 0.85 95%CI = 0.78–0.93). Odds of attending screening were lower for women in the most deprived (uptake = 49%, OR = 0.54, 95%CI = 0.46–0.62) in comparison with the least deprived quintile (uptake = 71%). Odds of attendance also increased if the woman had ever previously attended (OR 3.9 95% CI 3.5–4.4), and decreased with each year of increasing age (OR 0.96 95% CI 0.96–0.97). There were no interactions between any of the other predictors and whether the appointment was before or after publication of the Marmot review. Conclusion: No change in uptake of breast cancer screening above normal seasonal variation was detected after publication of the Marmot review

How effective are digital interventions in increasing flu vaccination amongst pregnant women? A systematic review protocol

Pregnant women and their unborn babies are at increased risk of complications as a result of flu, yet uptake of the flu vaccination in the UK remains low. Digital interventions have proven effectiveness in changing health behaviour, but their effectiveness in increasing flu vaccination amongst pregnant women has not been examined. This protocol details the design and methodology of a systematic review and meta-analysis, examining the effectiveness of digital interventions in increasing flu vaccination amongst pregnant women. Methods: Bibliographic databases will be searched using appropriate search terms related to vaccination, pregnancy and flu. Randomised, non-randomised, quasi randomised controlled trials and other quantitative study designs will be eligible for inclusion, and studies will present the rate of flu vaccination amongst pregnant women of digital interventions compared to non-digital interventions, or usual care. No date or study country restrictions will be put on included studies, but studies will be published in English. Discussion: This is the first known systematic review to examine the effectiveness of digital interventions in increasing the rate of flu vaccination amongst pregnant women. This review has the potential to inform whether digital interventions are an appropriate and successful method of increasing flu vaccination amongst pregnant women, and to determine which mode of digital intervention is most effective. Trial registration: This systematic review is registered on the international prospective register of systematic reviews (PROSPERO). Registration number pending

Measurement properties of the Disability Rating Index in patients undergoing hip replacement

Objective. The aim of this study was to establish and validate the measurement properties of the Disability Rating Index (DRI) in a population of adults undergoing hip replacement. Methods. One hundred and twenty-six adults participating in a randomized controlled trial completed the Oxford Hip Score, Harris Hip Score, DRI and EuroQol Group–Five Dimensions (EQ-5D) questionnaires at four time points. The structural validity of the DRI was assessed using principal component analysis. Cronbach’s α was used to determine the internal consistency and scale reliability was also assessed. Correlation between the DRI and the other functional and health-related quality of life scales was used to check criterion validity. DRI responsiveness was estimated and the interpretability of the scale was also assessed by checking for edge effects. Results. Results of analyses showed that the DRI was internally consistent (Cronbach’s α = 0.92), had good association with both function-specific and general health-related quality of life scores and was sensitive to change (smallest detectable change = 2.7). No evidence of edge effects was found. Furthermore, structural assessment of the DRI revealed two novel subscales representing simple tasks and difficult tasks. Conclusions. The DRI is structurally valid, responsive and concurs with functional assessment in adults undergoing hip replacement

An adaptive two-arm clinical trial using early endpoints to inform decision making : design for a study of sub-acromial spacers for repair of rotator cuff tendon tears

Background There is widespread concern across the clinical and research communities that clinical trials, powered for patient-reported outcomes, testing new surgical procedures are often expensive and time-consuming, particularly when the new intervention is shown to be no better than the standard. Conventional (non-adaptive) randomised controlled trials (RCTs) are perceived as being particularly inefficient in this setting. Therefore, we have developed an adaptive group sequential design that allows early endpoints to inform decision making and show, through simulations and a worked example, that these designs are feasible and often preferable to conventional non-adaptive designs. The methodology is motivated by an ongoing clinical trial investigating a saline-filled balloon, inserted above the main joint of the shoulder at the end of arthroscopic debridement, for treatment of tears of rotor cuff tendons. This research question and setting is typical of many studies undertaken to assess new surgical procedures. Methods Test statistics are presented based on the setting of two early outcomes, and methods for estimation of sequential stopping boundaries are described. A framework for the implementation of simulations to evaluate design characteristics is also described. Results Simulations show that designs with one, two and three early looks are feasible and, with appropriately chosen futility stopping boundaries, have appealing design characteristics. A number of possible design options are described that have good power and a high probability of stopping for futility if there is no evidence of a treatment effect at early looks. A worked example, with code in R, provides a practical demonstration of how the design might work in a real study. Conclusions In summary, we show that adaptive designs are feasible and could work in practice. We describe the operating characteristics of the designs and provide guidelines for appropriate values for the stopping boundaries for the START:REACTS (Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery) study

Ethnicity and detention : are black and minority ethnic (BME) groups disproportionately detained under the Mental Health Act 2007?

Purpose There is substantial evidence to suggest that Black and minority ethnic (BME) patients are disproportionately detained under the Mental Health Act (MHA). We examined ethnic differences in patients assessed for detention and explored the effect of ethnicity after controlling for confounders. Methods A prospective study of all MHA assessments conducted in 1 year (April 2009–March 2010) within Birmingham and Solihull Mental Health Foundation Trust, UK. Proportion of assessments and detentions within denominator population of service users and regional populations were calculated. Multiple regression analysis was conducted to determine which variables were associated with the outcome of MHA assessment and the role of ethnicity. Results Of the 1115 assessments, 709 led to detentions (63.58 %). BME ethnic groups were statistically more likely to be assessed and detained under the MHA as compared to Whites, both in the service user and the ethnic population estimates in Birmingham, UK. MHA detention was predicted by having a serious mental illness, the presence of risk, older age and living alone. Ethnicity was not associated with detention under the MHA with age, diagnosis, risk and level of social support accounted for. Conclusion The BME ‘disproportionality’ in detention rates seems to be due to higher rates of mental illness, greater risk and poorer levels of social support rather than ethnicity per se

Assessing fatigue in adults with Axial Spondyloarthritis : a systematic review of the quality and acceptability of patient-reported outcome measures

Objective Evaluate the quality and acceptability of patient-reported outcome measures used to assess fatigue in patients with Axial Spondyloarthritis. Methods A two-stage systematic review of major electronic databases (1980-2017) to: 1) Identify measures; and 2) Identify evaluative studies. Study and measurement quality was evaluated following international standards. Measurement content was appraised against a conceptual model of RA-fatigue. Results From 387 reviewed abstracts, 23 articles provided evidence for nine fatigue-specific measures: six multi-item and three single-item. No axSpA-fatigue specific measure was identified. Evidence of reliability was limited, but acceptable for the Multi-dimensional Fatigue Inventory (internal consistency, test-retest) and Short Form 36-item Health Survey Vitality subscale (SF-36 VT) (internal consistency). Evidence of construct validity was moderate for the Functional Assessment of Chronic Illness Therapy-Fatigue and 10cm visual analogue scale, limited for the SF-36 VT, and not available for the remaining measures. Responsiveness was rarely evaluated. Evidence of measurement error, content validity or structural validity was not identified. Most measures provide a limited reflection of fatigue; the most comprehensive were the Multi-dimensional Assessment of Fatigue (MAF), MFI-20, FACIT-fatigue and Fatigue Severity Scale (FSS). Conclusion The limited content and often poor quality of the reviewed measures limits any clear recommendation for fatigue-assessment in this population; assessments should be applied with caution until further robust evidence is established. Well developed, patient-derived measures can provide essential evidence of the patient’s perspective to inform clinical research and drive tailored healthcare. The collaborative engagement of key stakeholders must seek to ensure that future fatigue assessment is relevant, acceptable and of high quality

Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS) : statistical analysis plan

Statistical Analysis Plan (SAP) for the Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS) Trial. This SAP describes the detailed statistical analysis plan for the START:REACTS study as agreed by the DMC and approved by the Chief Investigator prior to analyses taking place. START:REACTS is a multi-centre randomised controlled trial to assess the difference in clinical and cost effectiveness between arthroscopic debridement of the subacromial space and arthroscopic debridement with insertion of an InSpace balloon (Stryker, USA). More details can be found on the study website https://warwick.ac.uk/fac/sci/med/research/ctu/trials/startreacts START:REACTS is a ISRCTN registered clinical trial ISRCTN17825590 (https://www.isrctn.com/ISRCTN17825590) and was funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership

Protocol for a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus single-agent femoral nerve blockade as analgesia for total knee arthroplasty: Perioperative Analgesia for Knee Arthroplasty (PAKA)

Introduction: Total knee arthroplasty (TKA) surgery causes postoperative pain. The use of perioperative injections around the knee containing local anaesthetic, opiates and non-steroidal anti-inflammatory drugs has increased in popularity to manage pain. Theoretical advantages include reduced requirements for analgesia and earlier mobilisation. We propose a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus femoral nerve anaesthetic blockade as analgesia for TKA. The aim is to determine, in patients undergoing TKA, if there is a difference in patient-reported pain scores on the visual analogue scale (VAS) prior to physiotherapy on day 1 postoperatively between treatment groups. Methods and analysis: Patients undergoing a primary unilateral TKA at University Hospitals Coventry and Warwickshire Hospitals will be assessed for eligibility. A total of 264 patients will provide 90% power to detect a difference of 12 mm on the VAS on day 1 postoperatively at the 5% level. The trial will use 1:1 randomisation, stratified by mode of anaesthetic. Primary outcome measure will be the VAS for pain prior to physiotherapy on day 1. Secondary outcome measures include VAS on day 2, total use of opiate analgesia up to 48 h, ordinal pain scores up to 40 min after surgery, independent functional knee physiotherapist assessment on days 1 and 2. Oxford knee Scores (OKS), EuroQol (EQ-5D) and Douleur Neuropathic Pain Scores (DN2) will be recorded at baseline, 6 weeks and 12 months. Adverse events will be recorded up to 12 months. Analysis will investigate differences in VAS on day 1 between the two treatment groups on an intention-to-treat basis. Tests will be two-sided and considered to provide evidence for a significant difference if p values are less than 0.05. Ethics and dissemination: NRES Committee West Midlands, 23 September 2013 (ref: 13/WM/0316). The results will be disseminated via peer-reviewed publications and conference presentations. Trial registration numbers: ISRCTN 60611146 and EUDRACT Number 2013-002439-10 (protocol code number PAKA-33601-AS117013); Pre-results