P Royston

..However, the normality assumption may not be appropriate for all the parameters of interest when analysing prognostic modelling studies, such as predicted survival probabilities and model performance measures...

..Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model...

..Dichotomization of continuous data is unnecessary for statistical analysis and in particular should not be applied to explanatory variables in regression models...

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..The intermediate outcome measure is progression-free survival. An international randomized controlled trial using the new design is already under way...

..We demonstrate the ability of the approach to detect and display treatment/covariate interactions in two examples from controlled trials in cancer...

..The tools described here may be a step towards providing greater insight into the natural history of the disease and into possible underlying causes of clinical events. We illustrate these aspects by using the two examples in cancer...

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..For the cases considered the grid tests are always inferior to the Q- and B- tests...

..We study the properties of the measure by simulation and by example in three substantial data sets. We believe that our new measure will prove useful as a tool to evaluate the separation available-with a prognostic model...

..The scope of the method is illustrated by fitting models to several real data sets and assessing each model using goodness-of-fit techniques...

..To speed up the evaluation of new therapies, the multi-arm, multi-stage trial design was suggested previously by the authors...

..Since our results are derived from flexible statistical models, they may be interpreted as a new hypothesis and require validation in independent data...

..The traditional method of analysing continuous or ordinal risk factors by categorization or linear models may be improved...

..6 months (high risk). Our approach, based on categorising a continuous prognostic index produced by the MFP algorithm, allowed more flexibility in the determination of risk groups than traditional approaches...

..The results show that the other measures perform poorly, primarily because they are affected either by the degree of censoring or the follow-up period...

..Despite the considerable flexibility of the family of fractional polynomials and the consequent risk of overfitting when several variables are considered, we conclude that the multivariable selection algorithm can find stable models...

..Estimates of the probability of conception during the most fertile period of the cycle and of the effects of covariates are similar to estimates found using standard models...

..Our investigations suggest that ART is the first software to allow incorporation of all these elements. Further extensions to the methodology such as non-local alternatives for the logrank test are also considered...

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..The detection rate of screening by a combination of maternal factors and the measurement of cervical length was substantially higher than that of screening by each method alone...

..Non-linear time-fixed effects are found for progesterone receptor status and number of positive lymph nodes. Highly statistically significant time-varying effects are present for progesterone receptor status and tumour size...

..While acknowledging that further research is needed, we argue why MFP is our preferred approach for multivariable model building with continuous covariates...

..We analyzed the effect of histology and various clinical and laboratory predictors in a new continuous prognostic index for metastatic renal-cell carcinoma based on fractional polynomials...

..To conclude, a discussion of the future of modelling and the future of the bootstrap is given...

..By using intermediate outcomes and testing a number of new agents (and combinations) simultaneously, the new design requires fewer patients. Three trials using this methodology are presented...

..These graphs of the distribution of survival times for individuals in each study group, which are simple to produce, may usefully complement Kaplan-Meier plots...

..Optimizing the Akaike information criterion appears to be appropriate for choosing the degree of simplification...

..The objective is to validate the model on independent data from CASCADE...

..Model development and validation processes are not always linked to the clinical aim of the model, which may affect their clinical validity. We make some suggestions in this review for improvement in methodology and reporting...

..MICE was amongst the best performing multiple imputation methods with regards to the quality of the predictions. Additionally, it produced the least biased estimates, with good coverage, and hence is recommended for use in practice...

..The methods are illustrated by using a model developed to predict progression to a new AIDS event or death in HIV-1 positive patients starting antiretroviral therapy...

..It is simple to use, includes routinely collected variables, and provides a useful tool for patient advice and institutional comparisons...

..A checklist highlighting the important considerations when designing a simulation study is provided. A small review of the literature identifies the current practices within published simulation studies...