Firth's logistic regression has become a standard approach for the analysis of binary outcomes with small samples. Whereas it reduces the bias in maximum likelihood estimates of coefficients, bias towards one-half is introduced in the predicted probabilities. The stronger the imbalance of the outcome, the more severe is the bias in the predicted probabilities. We propose two simple modifications of Firth's logistic regression resulting in unbiased predicted probabilities. The first corrects the predicted probabilities by a post hoc adjustment of the intercept. The other is based on an alternative formulation of Firth's penalization as an iterative data augmentation procedure. Our suggested modification consists in introducing an indicator variable that distinguishes between original and pseudo-observations in the augmented data. In a comprehensive simulation study, these approaches are compared with other attempts to improve predictions based on Firth's penalization and to other published penalization strategies intended for routine use. For instance, we consider a recently suggested compromise between maximum likelihood and Firth's logistic regression. Simulation results are scrutinized with regard to prediction and effect estimation. We find that both our suggested methods do not only give unbiased predicted probabilities but also improve the accuracy conditional on explanatory variables compared with Firth's penalization. While one method results in effect estimates identical to those of Firth's penalization, the other introduces some bias, but this is compensated by a decrease in the mean squared error. Finally, all methods considered are illustrated and compared for a study on arterial closure devices in minimally invasive cardiac surgery. Copyright © 2017 John Wiley & Sons, Ltd.

Separation is encountered in regression models with a discrete outcome (such as logistic regression) where the covariates perfectly predict the outcome. It is most frequent under the same conditions that lead to small-sample and sparse-data bias, such as presence of a rare outcome, rare exposures, highly correlated covariates, or covariates with strong effects. In theory, separation will produce infinite estimates for some coefficients. In practice, however, separation may be unnoticed or mishandled because of software limits in recognizing and handling the problem and in notifying the user. We discuss causes of separation in logistic regression and describe how common software packages deal with it. We then describe methods that remove separation, focusing on the same penalized-likelihood techniques used to address more general sparse-data problems. These methods improve accuracy, avoid software problems, and allow interpretation as Bayesian analyses with weakly informative priors. We discuss likelihood penalties, including some that can be implemented easily with any software package, and their relative advantages and disadvantages. We provide an illustration of ideas and methods using data from a case-control study of contraceptive practices and urinary tract infection.

Due to the increase in prevalence of diabetes and CKD5, the costs of renal therapy are expected to rise. We believe that these data may help health-care policy makers to make informed decisions.