Treatment compliance and effectiveness of a cognitive behavioural intervention for low back pain : a complier average causal effect approach to the BeST data set

Background: Group cognitive behavioural intervention (CBI) is effective in reducing low-back pain and disability in comparison to advice in primary care. The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance. Methods: In this multicentre trial, 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices. Participants were randomised to advice (control n = 233) or advice plus CBI (n = 468). Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment. We estimated the complier average causal effect (CACE) of treatment. Results: Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat (ITT) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire (CACE: 1.6 points, 95% CI 0.51 to 2.74; ITT: 1.3 points, 95% CI 0.55 to 2.07), the Modified Von Korff disability score (CACE: 12.1 points, 95% CI 6.07 to 18.17; ITT: 8.6 points, 95% CI 4.58 to 12.64) and the Modified von Korff pain score (CACE: 10.4 points, 95% CI 4.64 to 16.10; ITT: 7.0 points, 95% CI 3.26 to 10.74). People who were non-compliant were younger and had higher pain scores at randomisation. Conclusions: Treatment compliance is important in the effectiveness of group CBI. Younger people and those with more pain are at greater risk of non-compliance

Current practice in methodology and reporting of the sample size calculation in randomised trials of hip and knee osteoarthritis: a protocol for a systematic review

Background A key aspect of the design of randomised controlled trials (RCTs) is determining the sample size. It is important that the trial sample size is appropriately calculated. The required sample size will differ by clinical area, for instance, due to the prevalence of the condition and the choice of primary outcome. Additionally, it will depend upon the choice of target difference assumed in the calculation. Focussing upon the hip and knee osteoarthritis population, this study aims to systematically review how the trial size was determined for trials of osteoarthritis, on what basis, and how well these aspects are reported. Methods Several electronic databases (Medline, Cochrane library, CINAHL, EMBASE, PsycINFO, PEDro and AMED) will be searched to identify articles on RCTs of hip and knee osteoarthritis published in 2016. Articles will be screened for eligibility and data extracted independently by two reviewers. Data will be extracted on study characteristics (design, population, intervention and control treatments), primary outcome, chosen sample size and justification, parameters used to calculate the sample size (including treatment effect in control arm, level of variability in primary outcome, loss to follow-up rates). Data will be summarised across the studies using appropriate summary statistics (e.g. n and %, median and interquartile range). The proportion of studies which report each key component of the sample size calculation will be presented. The reproducibility of the sample size calculation will be tested. Discussion The findings of this systematic review will summarise the current practice for sample size calculation in trials of hip and knee osteoarthritis. It will also provide evidence on the completeness of the reporting of the sample size calculation, reproducibility of the chosen sample size and the basis for the values used in the calculation. Trial registration As this review was not eligible to be registered on PROSPERO, the summary information was uploaded to Figshare to make it publicly accessible in order to avoid unnecessary duplication amongst other benefits (https://doi.org/10.6084/m9.figshare.5009027.v1); Registered January 17, 2017

Cost effectiveness of treatment with percutaneous Kirschner wires versus volar locking plate for adult patients with a dorsally displaced fracture of the distal radius: Analysis from the DRAFFT trial

We present an economic evaluation using data from the Distal Radius Acute Fracture Fixation Trial (DRAFFT) to compare the relative cost effectiveness of percutaneous Kirschner wire (K-wire) fixation and volar locking-plate fixation for patients with dorsally-displaced fractures of the distal radius. The cost effectiveness analysis (cost per quality-adjusted life year; QALY) was derived from a multi-centre, two-arm, parallel group, assessor-blind, randomised controlled trial which took place in 18 trauma centres in the United Kingdom. Data from 460 patients were available for analysis, which includes both a National Health Service cost perspective including costs of surgery, implants and healthcare resource use over a 12-month period after surgery, and a societal perspective, which includes the cost of time off work and the need for additional private care. There was only a small difference in QALYs gained for patients treated with locking-plate fixation over those treated with K-wires. At a mean additional cost of £714 (95% confidence interval 588 to 865) per patient, locking-plate fixation presented an incremental cost effectiveness ratio (ICER) of £89 322 per QALY within the first 12 months of treatment. Sensitivity analyses were undertaken to assess the ICER of locking-plate fixation compared with K-wires. These were greater than £30 000. Compared with locking-plate fixation, K-wire fixation is a 'cost saving' intervention, with similar health benefits

Problems persist in reporting of methods and results for the WOMAC measure in hip and knee osteoarthritis trials

Purpose The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a commonly used outcome measure for osteoarthritis. There are different versions of the WOMAC (Likert, visual analogue or numeric scales). A previous review of trials published before 2010 found poor reporting and inconsistency in how the WOMAC was used. This review explores whether these problems persist. Methods This systematic review included randomised trials of hip and/or knee osteoarthritis published in 2016 that used the WOMAC. Data were extracted on the version used, score range, analysis and results of the WOMAC, and whether these details were clearly reported. Results This review included 62 trials and 41 reported the WOMAC total score. The version used and item range for the WOMAC total score were unclear in 44% (n = 18/41) and 24% (n = 10/41) of trials, respectively. The smallest total score range was 0–10 (calculated by averaging 24 items scored 0–10); the largest was 0–2400 (calculated by summing 24 items scored 0–100). All trials reported the statistical analysis methods but only 29% reported the between-group mean difference and 95% confidence interval. Conclusion Details on the use and scoring of the WOMAC were often not reported. We recommend that trials report the version of the WOMAC and the score range used. The between-group treatment effect and corresponding confidence interval should be reported. If all the items of the WOMAC are collected, the total score and individual subscale scores should be presented. Better reporting would facilitate the interpretation, comparison and synthesis of the WOMAC score in trials

The 1983 drought in the West Sahel: a case study

Some drought years over sub-Saharan west Africa (1972, 1977, 1984) have been previously related to a cross-equatorial Atlantic gradient pattern with anomalously warm sea surface temperatures (SSTs) south of 10°N and anomalously cold SSTs north of 10°N. This SST dipole-like pattern was not characteristic of 1983, the third driest summer of the twentieth century in the Sahel. This study presents evidence that the dry conditions that persisted over the west Sahel in 1983 were mainly forced by high Indian Ocean SSTs that were probably remanent from the strong 1982/1983 El Niño event. The synchronous Pacific impact of the 1982/1983 El Niño event on west African rainfall was however, quite weak. Prior studies have mainly suggested that the Indian Ocean SSTs impact the decadal-scale rainfall variability over the west Sahel. This study demonstrates that the Indian Ocean also significantly affects inter-annual rainfall variability over the west Sahel and that it was the main forcing for the drought over the west Sahel in 1983

Intrarater reliability and agreement of linear encoder derived heel-rise endurance test outcome measures in healthy adults

publisher: Elsevier articletitle: Intrarater reliability and agreement of linear encoder derived heel-rise endurance test outcome measures in healthy adults journaltitle: Journal of Electromyography and Kinesiology articlelink: http://dx.doi.org/10.1016/j.jelekin.2017.07.004 content_type: article copyright: © 2017 Elsevier Ltd. All rights reserved

Bayesian adaptive designs for multi-arm trials: an orthopaedic case study

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The data used in this study were generated as part of the CAST study. Requests to share individual, de-identified participant data, aggregated data, data dictionaries, and other study documents from this study should be sent to the CAST Chief Investigator (SEL). Data sharing requests will be assessed on their individual merits. The FACTS files used to simulate the Bayesian adaptive designs are publicly available at https://github.com/egryan90/Bayesian-adaptive-designs-for-CAST-study-Ryan-et-al.-2019Background: Bayesian adaptive designs can be more efficient than traditional methods for multi‐arm randomised controlled trials. The aim of this work was to demonstrate how Bayesian adaptive designs can be constructed for multi‐arm phase III clinical trials and assess potential benefits that these designs offer. Methods: We constructed several alternative Bayesian adaptive designs for the Collaborative Ankle Support Trial (CAST), which was a randomised controlled trial that compared four treatments for severe ankle sprain. These incorporated response adaptive randomisation, arm dropping, and early stopping for efficacy or futility. We studied the Bayesian designs’ operating characteristics via simulation. We then virtually re‐executed the trial by implementing the Bayesian adaptive designs using patient data sampled from the CAST study to demonstrate the practical applicability of the designs. Results: We constructed five Bayesian adaptive designs, each of which had high power and recruited fewer patients on average than the original design’s target sample size. The virtual executions 2 showed that most of the Bayesian designs would have led to trials that declared superiority of one of the interventions over the control. Bayesian adaptive designs with RAR or arm dropping were more likely to allocate patients to better performing arms at each interim analysis. Similar estimates and conclusions were obtained from the Bayesian adaptive designs as from the original trial. Conclusions: Using CAST as an example, this case study showed how Bayesian adaptive designs can be constructed for phase III multi‐arm trials using clinically relevant decision criteria. These designs demonstrated that they can potentially generate earlier results and allocate more patients to betterperforming arms. We recommend the wider use of Bayesian adaptive approaches in phase III clinical trials.Medical Research Council (MRC)National Co‐ordinating Centre for Health Technology AssessmentNational Institute of Health Researc

Nonlinear dynamic measures of walking in healthy older adults: A systematic scoping review.

This is the final version. Available from MDPI via the DOI in this record. Data Availability Statement: Not applicableBACKGROUND: Maintaining a healthy gait into old age is key to preserving the quality of life and reducing the risk of falling. Nonlinear dynamic analyses (NDAs) are a promising method of identifying characteristics of people who are at risk of falling based on their movement patterns. However, there is a range of NDA measures reported in the literature. The aim of this review was to summarise the variety, characteristics and range of the nonlinear dynamic measurements used to distinguish the gait kinematics of healthy older adults and older adults at risk of falling. METHODS: Medline Ovid and Web of Science databases were searched. Forty-six papers were included for full-text review. Data extracted included participant and study design characteristics, fall risk assessment tools, analytical protocols and key results. RESULTS: Among all nonlinear dynamic measures, Lyapunov Exponent (LyE) was most common, followed by entropy and then Fouquet Multipliers (FMs) measures. LyE and Multiscale Entropy (MSE) measures distinguished between older and younger adults and fall-prone versus non-fall-prone older adults. FMs were a less sensitive measure for studying changes in older adults' gait. Methodology and data analysis procedures for estimating nonlinear dynamic measures differed greatly between studies and are a potential source of variability in cross-study comparisons and in generating reference values. CONCLUSION: Future studies should develop a standard procedure to apply and estimate LyE and entropy to quantify gait characteristics. This will enable the development of reference values in estimating the risk of falling

Bayesian adaptive designs for multi-arm trials: an orthopaedic case study

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The data used in this study were generated as part of the CAST study. Requests to share individual, de-identified participant data, aggregated data, data dictionaries, and other study documents from this study should be sent to the CAST Chief Investigator (SEL). Data sharing requests will be assessed on their individual merits. The FACTS files used to simulate the Bayesian adaptive designs are publicly available at https://github.com/egryan90/Bayesian-adaptive-designs-for-CAST-study-Ryan-et-al.-2019Background: Bayesian adaptive designs can be more efficient than traditional methods for multi‐arm randomised controlled trials. The aim of this work was to demonstrate how Bayesian adaptive designs can be constructed for multi‐arm phase III clinical trials and assess potential benefits that these designs offer. Methods: We constructed several alternative Bayesian adaptive designs for the Collaborative Ankle Support Trial (CAST), which was a randomised controlled trial that compared four treatments for severe ankle sprain. These incorporated response adaptive randomisation, arm dropping, and early stopping for efficacy or futility. We studied the Bayesian designs’ operating characteristics via simulation. We then virtually re‐executed the trial by implementing the Bayesian adaptive designs using patient data sampled from the CAST study to demonstrate the practical applicability of the designs. Results: We constructed five Bayesian adaptive designs, each of which had high power and recruited fewer patients on average than the original design’s target sample size. The virtual executions 2 showed that most of the Bayesian designs would have led to trials that declared superiority of one of the interventions over the control. Bayesian adaptive designs with RAR or arm dropping were more likely to allocate patients to better performing arms at each interim analysis. Similar estimates and conclusions were obtained from the Bayesian adaptive designs as from the original trial. Conclusions: Using CAST as an example, this case study showed how Bayesian adaptive designs can be constructed for phase III multi‐arm trials using clinically relevant decision criteria. These designs demonstrated that they can potentially generate earlier results and allocate more patients to betterperforming arms. We recommend the wider use of Bayesian adaptive approaches in phase III clinical trials.Medical Research Council (MRC)National Co‐ordinating Centre for Health Technology AssessmentNational Institute of Health Researc

Progressive functional exercise versus best practice advice for adults aged 50 years or over after ankle fracture: protocol for a pilot randomised controlled trial in the UK - the Ankle Fracture Treatment: Enhancing Rehabilitation (AFTER) study

Introduction Ankle fractures result in significant morbidity in adults, with prognosis worsening with increasing age. Previous trials have not found evidence supporting supervised physiotherapy sessions, but these studies have not focused on older adults or tailored the exercise interventions to the complex needs of this patient group. The Ankle Fracture Treatment: Enhancing Rehabilitation study is a pilot randomised controlled trial to assess feasibility of a later definitive trial comparing best-practice advice with progressive functional exercise for adults aged 50 years and over after ankle fracture. The main objectives are to assess: (i) patient engagement with the trial, measured by the participation rate of those eligible; (ii) establish whether the interventions are acceptable to participants and therapists, assessed by intervention adherence levels, participant interviews and a therapist focus group; (iii) participant retention in the trial, measured by the proportion of participants providing outcome data at 6 months; (iv) acceptability of measuring outcomes at 3 and 6 month follow-up. Methods and analysis A multicentre pilot randomised controlled trial with an embedded qualitative study. At least 48 patients aged 50 years and over with an ankle fracture requiring surgical management, or non-operative management by immobilisation for at least 4 weeks, will be recruited from a minimum of three National Health Service hospitals in the UK. Participants will be allocated 1:1 via a central web-based randomisation system to: (i) best-practice advice (one session of face-to-face self-management advice delivered by a physiotherapist and up to two optional additional sessions) or (ii) progressive functional exercise (up to six sessions of individual face-to-face physiotherapy). An embedded qualitative study will include one-to-one interviews with up to 20 participants and a therapist focus group. Ethics and dissemination Hampshire B Research Ethics Committee (18/SC/0281) gave approval on 2nd July 2018. Trial registration number ISRCTN1661233