S G Thompson

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..Researchers internationally are looking at the potential of Internet interventions in this area...

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..Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges...

..Using these methods, we can benefit from the advantages of Bayesian modelling of binary outcome data at the same time as providing results on a clinically interpretable scale...

..This is a discussion of the paper 'Making efficient use of patients in designing phase III trials investigating simultaneously a set of targeted therapies with different targets' by Werner Vach and Rene dePont Christensen...

..To assess whether the mortality benefit from screening men aged 65-74 for abdominal aortic aneurysm decreases over time, and to estimate the long term cost effectiveness of screening...

..Analysis of multinational cost data must recognise differences in mean, spread and skewness across centres, as well as the data's hierarchical structure...

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..Also, although meta-analyses generally summarise an intervention's effect as a relative risk reduction, the groups of patients with the greatest absolute risk reduction have the most to gain...

..The examples considered in this paper show the tension between the scientific rationale for using meta-regression and the difficult interpretative problems to which such analyses are prone...

..Cost data usually have very skewed distributions and can be difficult to model. The authors investigate whether choice of distribution can make a difference to the conclusions drawn...

..If a national screening programme for AAA were adopted in the UK, it would be expected to increase the elective and decrease the emergency surgical workload...

..CONCLUSION: A greater awareness of the benefits of full participation in a screening programme could provide a larger and sustained mortality reduction...

..We show how this can be achieved within a Bayesian analysis, while still recognizing the binary nature of the original outcome data...

..To provide reliable estimates of the long-term cost-effectiveness of abdominal aortic aneurysm screening in men...

..Investigating the sensitivity of conclusions to choice of model should thus be an essential component of analysing cost data in practice...

..The advantages and flexibility of a fully Bayesian approach to meta-analysis of binary outcome data, considered on an absolute risk or relative risk scale, are now available...

..Relative merits of the three software packages for such meta-analyses are discussed, as are the assessment of model assumptions and extensions to incorporate more than two treatments...

..We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease...

..Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality...

..Longer-term mortality benefit and cost-effectiveness for abdominal aortic aneurysm (AAA) screening are uncertain...

..There is also the opportunity to incorporate prior beliefs on likely values of the ICC. The methods are exemplified using data from a cluster randomized trial...

..The methods proposed enable available ICC information to be summarised appropriately by an informative prior distribution, which is of direct practical use in cluster randomized trials...

..We propose random effects models to allow for such clustering, across a range of contexts and trial designs, and investigate their effect on estimation and interpretation of the treatment effect...

..We examine how missing outcome data are handled in randomized controlled trials in order to assess whether adequate steps have been taken to reduce nonresponse bias and to identify ways to improve procedures for missing data...

..The methods are applied to an example of a cluster randomised trial in the prevention of coronary heart disease. The modelling strategy presented would also be useful in other situations involving hierarchical multivariate outcomes...

..In practical applications, the methods can be used to provide sensitivity analyses for the potential effects of multiple dissemination biases operating in meta-analysis...

..The method is applied to some real data sets and an extension to multivariate meta-regression is described...

..Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke...

..All models give similar estimates of the intervention effect and we conclude that non-response bias is likely to be small...

..The methods are illustrated in a randomized trial in community psychiatry...

..We show that a comparison of sample means is a reasonable choice in this case despite the skewness...

..The permutation test appropriately tempers the statistical significance of meta-regression findings. We recommend its use before a statistically significant relationship is claimed from a standard meta-regression analysis...

..Experience needs to be gained in applying these methods in practice, and using their results in decision making...

..The methods presented in this paper can be used by applied researchers to protect against loss of power, or to choose a design which reduces the impact of uncertainty in the ICC...

..One or both should be presented in published meta-analyses in preference to the test for heterogeneity...

..Data from the Multicentre Aneurysm Screening Study (MASS) are used to examine the influences of age and social deprivation in the context of screening for abdominal aortic aneurysms (AAAs)...

..Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes...

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..We conclude that inferences regarding the random effects can crucially depend on the assumptions made and recommend using a distribution, such as those suggested here, which is more flexible than the normal...

..Surveillance is a common management strategy for small abdominal aortic aneurysm (AAA) (3.0-5.4 cm in diameter). Individual characteristics, other than diameter, may influence aneurysm growth or rupture rates...

..Active follow up, for example every 3 months, is appropriate for men with an aortic diameter of 45-54 mm...

..The impact of heterogeneity, or use of random effects, are seldom discussed. There is thus considerable scope for enhancing the methods of analysis and presentation of IPD meta-analysis...

..We conclude that it is relevant to consider optimal designs under a range of hypotheses about the true response rate, and that allowing early stopping for efficacy is always advantageous in terms of expected sample size...

..Statistical methods that incorporate these aspects appeared in a handful of papers, and the more widespread adoption of these is desirable...

..To evaluate whether either angiotensin converting enzyme (ACE) inhibitors or other classes of antihypertensive drug attenuate or increase growth rates of small infrarenal abdominal aortic aneurysms...

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..CONCLUSIONS: Annual, or less frequent, surveillance intervals are safe for all AAAs < or =45 mm in diameter. Smoking increases AAA growth, but atherosclerosis plays a minor role...

..We conclude that the validity of assumptions underlying MLMs used in CEA need to be critically evaluated before reliable conclusions can be drawn...

..More generally, the methods described in this report have widespread applicability to quantifying regression dilution bias in repeatability data from multiple prospective studies...

..Study..

..8%) on nebivolol and 192 (18.1%) on placebo (HR 0.88, 95% CI 0.71-1.08; P=0.21). CONCLUSION: Nebivolol, a beta-blocker with vasodilating properties, is an effective and well-tolerated treatment for heart failure in the elderly...

..We conclude that total duration is an appropriate primary outcome for clinical trials, but that multi-state models deserve greater use as an informative secondary analysis...

..In conclusion, it is important that simulation studies of statistical methods for recurrent events include simulated data sets based upon a range of models for event generation...

..We conclude that using OLS models for assessing international variation can lead to incorrect inferences, and that MLMs are more appropriate for assessing why resource use and costs vary across centres...

..The benefit of ICM for patients with borderline intelligence is an isolated effect which should be interpreted cautiously until further data are available...

..There are no precise estimates of the rate of rupture of large abdominal aortic aneurysms (AAA). There is recent suspicion that anatomic suitability for endovascular repair may be associated with a decreased risk of AAA rupture...