Progression and Death as Competing Risks in Ovarian Cancer

Background: Progression of a cancer disease and dying without progression can be understood as competing risks. The Cause-Specific Hazards Model and the Fine and Gray model on cumulative incidences are common statistical models to handle this problem. The pseudo value approach by Andersen and Klein is also able to cope with competing risks. It is still unclear which model suits best in which situation.Methods: For a simulated dataset and a real data example of ovarian cancer patients who are exposed to progression and death the three models are examined. We compare the three models with regards to interpretation and modeling requirements.Results: In this study, the parameter estimates for the competing risks are similar from the Cause-Specific Hazards Model and the Fine and Gray model. The pseudo value approach yields divergent results which are heavily dependent on modeling details.Conclusions: The investigated approaches do not exclude each other but moreover complement one another. The pseudo value approach is an alternative that circumvents proportionality assumptions. As in all survival analyses, situations with low event rates should be interpreted carefully

Estimate risk difference and number needed to treat in survival analysis

The hazard ratio (HR) is a measure of instantaneous relative risk of an increase in one unit of the covariate of interest, which is widely reported in clinical researches involving time-to-event data. However, the measure fails to capture absolute risk reduction. Other measures such as number needed to treat (NNT) and risk difference (RD) provide another perspective on the effectiveness of an intervention, and can facilitate clinical decision making. The article aims to provide a step-by-step tutorial on how to compute RD and NNT in survival analysis with R. For simplicity, only one measure (RD or NNT) needs to be illustrated, because the other measure is a reverse of the illustrated one (NNT=1/RD). An artificial dataset is composed by using the survsim package. RD and NNT are estimated with Austin method after fitting a Cox-proportional hazard regression model. The confidence intervals can be estimated using bootstrap method. Alternatively, if the standard errors (SEs) of the survival probabilities of the treated and control group are given, confidence intervals can be estimated using algebraic calculations. The pseudo-value model provides another method to estimate RD and NNT. Details of R code and its output are shown and explained in the main text

Prediction of survival with alternative modeling techniques using pseudo values

Background: The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo values enable statistically appropriate analyses of survival outcomes when used in seven alternative modeling techniques. Methods: In this case study, we analyzed survival of 1282 Dutch patients with newly diagnosed Head and Neck Squamous Cell Carcinoma (HNSCC) with conventional Kaplan-Meier and Cox regression analysis. We subsequently calculated pseudo values to reflect the individual survival patterns. We used these pseudo values to compare recursive partitioning (RPART), neural nets (NNET), logistic regression (LR) general linear models (GLM) and three variants of support vector machines (SVM) with respect to dichotomous 60-month survival, and continuous pseudo values at 60 months or estimated survival time. We used the area under the ROC curve (AUC) and the root of the mean squared error (RMSE) to compare the performance of these models using bootstrap validation. Results: Of a total of 1282 patients, 986 patients died during a median follow-up of 66 months (60-month survival: 52% [95% CI: 50%-55%]). The L

Incorporating longitudinal biomarkers for dynamic risk prediction in the era of big data: A pseudo‐observation approach

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163461/3/sim8687.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163461/2/sim8687-sup-0001-supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163461/1/sim8687_am.pd

SAS and R functions to compute pseudo-values for censored data regression

Recently, in a series of papers, a method based on pseudo-values has been proposed for direct regression modeling of the survival function, the restricted mean and cumulative incidence function with right censored data. The models, once the pseudo-values have been computed, can be fit using standard generalized estimating equation software. Here we present SAS macros and R functions to compute these pseudo-values. We illustrate the use of these routines and show how to obtain regression estimates for a study of bone marrow transplant patients

Analysis of survival data with cure fraction and variable selection: A pseudo-observations approach

In biomedical studies, survival data with a cure fraction (the proportion of subjects cured of disease) are commonly encountered. The mixture cure and bounded cumulative hazard models are two main types of cure fraction models when analyzing survival data with long-term survivors. In this article, in the framework of the Cox proportional hazards mixture cure model and bounded cumulative hazard model, we propose several estimators utilizing pseudo-observations to assess the effects of covariates on the cure rate and the risk of having the event of interest for survival data with a cure fraction. A variable selection procedure is also presented based on the pseudo-observations using penalized generalized estimating equations for proportional hazards mixture cure and bounded cumulative hazard models. Extensive simulation studies are conducted to examine the proposed methods. The proposed technique is demonstrated through applications to a melanoma study and a dental data set with high-dimensional covariates