Accounting for centre-effects in multicentre trials with a binary outcome – when, why, and how?

Open Access Research article Accounting for centre-effects in multicentre trials with a binary outcome – when, why, and how? Brennan C Kahan Correspondence: Brennan C Kahan [email protected] Author Affiliations Pragmatic Clinical Trials Unit, Queen Mary University of London, 58 Turner Street, London E1 2AB, UK MRC Clinical Trials Unit at UCL, 125 Kingsway, London WC2B 6NH, UK BMC Medical Research Methodology 2014, 14:20 doi:10.1186/1471-2288-14-20 The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2288/14/20 Received: 5 July 2013 Accepted: 3 February 2014 Published: 10 February 2014 © 2014 Kahan; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Formula display: Abstract Background It is often desirable to account for centre-effects in the analysis of multicentre randomised trials, however it is unclear which analysis methods are best in trials with a binary outcome. Methods We compared the performance of four methods of analysis (fixed-effects models, random-effects models, generalised estimating equations (GEE), and Mantel-Haenszel) using a re-analysis of a previously reported randomised trial (MIST2) and a large simulation study. Results The re-analysis of MIST2 found that fixed-effects and Mantel-Haenszel led to many patients being dropped from the analysis due to over-stratification (up to 69% dropped for Mantel-Haenszel, and up to 33% dropped for fixed-effects). Conversely, random-effects and GEE included all patients in the analysis, however GEE did not reach convergence. Estimated treatment effects and p-values were highly variable across different analysis methods. The simulation study found that most methods of analysis performed well with a small number of centres. With a large number of centres, fixed-effects led to biased estimates and inflated type I error rates in many situations, and Mantel-Haenszel lost power compared to other analysis methods in some situations. Conversely, both random-effects and GEE gave nominal type I error rates and good power across all scenarios, and were usually as good as or better than either fixed-effects or Mantel-Haenszel. However, this was only true for GEEs with non-robust standard errors (SEs); using a robust ‘sandwich’ estimator led to inflated type I error rates across most scenarios. Conclusions With a small number of centres, we recommend the use of fixed-effects, random-effects, or GEE with non-robust SEs. Random-effects and GEE with non-robust SEs should be used with a moderate or large number of centres

Efficiency of Health Care Sector at Sub-State Level in India: A Case of Punjab

In recent years, WHO and other individual researchers have advocated estimation of health system performance through stochastic frontier models. It provides an idealized yardstick to evaluate economic performance of health system. So far attempts in India have remained focused at state level analysis. This paper attempts a sub-state level analysis for an affluent Indian state, namely Punjab, by using stochastic frontier technique. Our results provide pertinent insight into state health system and facilitate health facility planning at the sub-state level. Carried out in two stages of estimation, our results suggest that life expectancy in the Indian state could be enhanced considerably by correcting the factors that are adversely influencing the sub-state level health system efficiency. A higher budgetary allocation for health manpower is recommended by us to improve efficiency in poorly performing districts. This may be supported by policy initiatives outside the health system by empowering women through better education and work participatio

Accommodating disability in higher education: a closer look at the evidence for a mainstream framework of learning support

In a recently published research article in this journal, Avramidis & Skidmore (2004) argued that it is time we placed issues of disability provision more in the context of provision for the generic student. They presented a study based on the Learning for All Questionnaire (LfAQ), which investigated certain implied issues. Findings indicated a need for improved educational provision for all students. No differences were found between disabled and non-disabled students in perceived level of needs or support for university, tutoring and lecturing systems. This null finding was the same for the learning support needs of disabled versus non-disabled students, with both groups wanting identical changes to the way the university's central learning support service responds to learning needs. These findings were taken as calling for a move away from a ‘specialist’ framework of disability provision and towards a ‘mainstream’ framework instead, in which the needs of disabled students are accommodated within improvements made in learning for all. Further, the Disabled Students' Allowance should be given over to departments in order to help fund this change in ‘institutional habitus’. In this article, four serious failings of the study and analyses are outlined. When these are addressed in a disability-theoretic reanalysis of the LfAQ data, every main finding is reversed. It is concluded that educational provisions are generally adequate. Students would welcome changes but these are more to do with increasing levels of convenience rather than learning support issues. Furthermore, the LfAQ data actually refute rather than support a mainstream framework of disability provision

Optimisation of system dynamics models

1. Definition of the Subject and Its Importance 2. Optimisation as calibration 3. Optimisation of performance (policy optimisation) 4. Examples of SD optimisation reported in the literature 5. Future directions in SD optimisation 6. Reference

Some results from a system dynamics model of construction sector competitiveness

Despite government-led good practice initiatives aimed to improve competitiveness in the U.K. construction sector, fluctuations in growth-driven demand, investment and constant regulatory revisions make it very difficult for an enterprise to plan strategically and remain competitive over a timescale exceeding 2 to 3 years. Research has been carried out to understand the historical evolution and changing face of the construction sector and the dynamic capabilities needed for an enterprise to secure a more sustainable competitive future. A dynamic model of a typical contracting firm has been created based upon extensive knowledge capture arising from fieldwork in collaborating firms together with a detailed review of the literature. A construct called the competitive index is used to model contract allocation in a stylised market. The simulations presented enable contracting enterprises to reflect strategically with a view to remaining competitive over a much longer time horizon of between 15 and 20 years. The rehearsal of strategy through simulated scenarios helps to minimise unexpected behaviour and offers insights about how endogenous behaviour can shape the future of the enterprise. To date, work on construction competitiveness has been either of a static nature or set predominantly at the level of the project. This study offers a new perspective by providing a dynamic tool to analyse competitiveness. It creates a new paradigm to support enhanced construction sector performance

Education Program using Non-Pharmacologic Support during Benzodiazepine Reduction in Patients with Anxiety Disorders

A private mental health clinic developed an initiative to aid patients with anxiety disorders to taper their use of benzodiazepines. Based on best practices, a treatment protocol was developed in which patients attended 4 sessions (1 per month) in which they combined instruction in non-pharmaceutical anti-anxiety techniques (guided imagery, mindfulness meditation, deep breathing, progressive muscle relaxation, exercise, emotional freedom) with cognitive behavioral therapy and use of selective serotonin re uptake inhibitors. Participants experienced a reduction in benzodiazepine use. This small scale initiative showed that the holistic approach to anxiety management was an effective plan to decrease the use of benzodiazepines in the treatment of anxiety disorder

A child-centred exploration of the relevance of family and friends to theory of mind development

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 The Authors.Theory of Mind (ToM) is said to develop at around 4 years old. But some studies suggest it develops considerably earlier than this, with others suggesting it develops much later. Although several recent studies have found that social factors (like gender, family size, number of siblings, and number of friends) can impact on ToM, other studies contradict those findings. We wondered whether addressing several procedural issues and ensuring the task concerns real protagonists in real time, would bear on the above issues. Here, 114 children of 3–6 years completed four ToM tasks incorporating controls from experimental psychology, including randomly varying the order of ToM and non-ToM questions across participants. Now, children passed ToM tasks from around 5 years old, rather than 4 years or earlier. Girls did not develop ToM any earlier than boys. There was clear correlational evidence for the older-sibling effect and effects of friends but no reliable effects of nuclear or extended family. However, when these factors were set in the context of one another, the sibling effect was driven by a negative influence from younger siblings (as opposed to older siblings) and the friends effect was driven by friends at school (as opposed to friends at home). Finally, “friends” was a stronger predictor than siblings but memory (a cognitive factor) and age (a maturational factor) were the strongest predictors of all

Factors and processes in children's transitive deductions

Transitive tasks are important for understanding how children develop socio-cognitively. However, developmental research has been restricted largely to questions surrounding maturation. We asked 6-, 7- and 8-year-olds (N = 117) to solve a composite of five different transitive tasks. Tasks included conditions asking about item-C (associated with the marked relation) in addition to the usual case of asking only about item-A (associated with the unmarked relation). Here, children found resolving item-C much easier than resolving item-A, a finding running counter to long-standing assumptions about transitive reasoning. Considering gender perhaps for the first time, boys exhibited higher transitive scores than girls overall. Finally, analysing in the context of one recent and well-specified theory of spatial transitive reasoning, we generated the prediction that reporting the full series should be easier than deducing any one item from that series. This prediction was not upheld. We discuss amendments necessary to accommodate all our earlier findings