Bmc Med Res Methodol
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Bmc Med Res Methodol · Jan 2014
Bayesian designs of phase II oncology trials to select maximum effective dose assuming monotonic dose-response relationship.
For many molecularly targeted agents, the probability of response may be assumed to either increase or increase and then plateau in the tested dose range. Therefore, identifying the maximum effective dose, defined as the lowest dose that achieves a pre-specified target response and beyond which improvement in the response is unlikely, becomes increasingly important. Recently, a class of Bayesian designs for single-arm phase II clinical trials based on hypothesis tests and nonlocal alternative prior densities has been proposed and shown to outperform common Bayesian designs based on posterior credible intervals and common frequentist designs. We extend this and related approaches to the design of phase II oncology trials, with the goal of identifying the maximum effective dose among a small number of pre-specified doses. ⋯ The use of Bayesian hypothesis tests and nonlocal alternative priors under ordering constraints between dose groups results in a robust performance of the design, which is thus superior to other common designs.
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Bmc Med Res Methodol · Jan 2014
Comparative StudyIdentifying unusual performance in Australian and New Zealand intensive care units from 2000 to 2010.
The Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD) collects voluntary data on patient admissions to Australian and New Zealand intensive care units (ICUs). This paper presents an in-depth statistical analysis of risk-adjusted mortality of ICU admissions from 2000 to 2010 for the purpose of identifying ICUs with unusual performance. ⋯ The statistical approach proposed in this paper is intended to be used for the review of observed ICU and hospital mortality. Two important messages from our study are firstly, that comprehensive risk-adjustment is essential in modelling patient mortality for comparing performance, and secondly, that the appropriate statistical analysis is complicated.
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Bmc Med Res Methodol · Jan 2014
The thresholds for statistical and clinical significance - a five-step procedure for evaluation of intervention effects in randomised clinical trials.
Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore, assessment of intervention effects in randomised clinical trials deserves more rigour in order to become more valid. ⋯ If the proposed five-step procedure is followed, this may increase the validity of assessments of intervention effects in randomised clinical trials.
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Bmc Med Res Methodol · Jan 2014
A comparison of three clustering methods for finding subgroups in MRI, SMS or clinical data: SPSS TwoStep Cluster analysis, Latent Gold and SNOB.
There are various methodological approaches to identifying clinically important subgroups and one method is to identify clusters of characteristics that differentiate people in cross-sectional and/or longitudinal data using Cluster Analysis (CA) or Latent Class Analysis (LCA). There is a scarcity of head-to-head comparisons that can inform the choice of which clustering method might be suitable for particular clinical datasets and research questions. Therefore, the aim of this study was to perform a head-to-head comparison of three commonly available methods (SPSS TwoStep CA, Latent Gold LCA and SNOB LCA). ⋯ Our subjective judgement was that Latent Gold offered the best balance of sensitivity to subgroups, ease of use and presentation of results with these datasets but we recognise that different clustering methods may suit other types of data and clinical research questions.
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Bmc Med Res Methodol · Jan 2014
ReviewHandling missing data in RCTs; a review of the top medical journals.
Missing outcome data is a threat to the validity of treatment effect estimates in randomized controlled trials. We aimed to evaluate the extent, handling, and sensitivity analysis of missing data and intention-to-treat (ITT) analysis of randomized controlled trials (RCTs) in top tier medical journals, and compare our findings with previous reviews related to missing data and ITT in RCTs. ⋯ Missing outcome data continues to be a common problem in RCTs. Definitions of the ITT approach remain inconsistent across trials. A large gap is apparent between statistical methods research related to missing data and use of these methods in application settings, including RCTs in top medical journals.