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Type Package Package prognosticroc February 20, 2015 Title Prognostic ROC curves for evaluating the predictive capacity of a binary test Version 0.7 Date 2013-11-27 Author Y. Foucher <Yohann.Foucher@univ-nantes.fr> and C. Combescure <Christophe.Combescure@hcuge.ch> Maintainer Y. Foucher <Yohann.Foucher@univ-nantes.fr> Description Prognostic ROC curve is an alternative graphical approach to represent the discriminative capacity of the marker: a receiver operating characteristic (ROC) curve by plotting 1 minus the survival in the high-risk group against 1 minus the survival in the lowrisk group. This package contains functions to assess prognostic ROC curve. The user can enter the survival according to a model previously estimated or the user can also enter individual survival data for estimating the prognostic ROC curve by using Kaplan-Meier estimator. The area under the curve (AUC) corresponds to the probability that a patient in the lowrisk group has a longer lifetime than a patient in the high-risk group. The prognostic ROC curve provides complementary information compared to survival curves. The AUC is assessed by using the trapezoidal rules. When survival curves do not reach 0, the prognostic ROC curve is incomplete and the extrapolations of the AUC are performed by assuming pessimist, optimist and non-informative situations. License GPL (>= 2) LazyLoad yes Depends splines, survival URL www.r-project.org, www.divat.fr NeedsCompilation no Repository CRAN Date/Publication 2013-11-27 17:03:15 R topics documented: prognosticroc-package.................................. 2 AggregatedPROC...................................... 3 IndividualPROC....................................... 4 1

2 prognosticroc-package Index 7 prognosticroc-package Prognostic ROC curves Description Details This package computes prognostic ROC curves. The separation between two survival curves represents the magnitude of the association between the intervention and the time-to-event. A statistical test can determine the statistical significance of the difference but does not quantify its magnitude. The purpose of the prognostic ROC curve is to represent this uncertainty: the AUC is the probability that the time-to-event is improved in one arm compared to the other. This package is designed for computing such prognostic ROC curve with confidence intervals obtained by bootstrap resampling (from individual data only). Package: Type: Version: 0.7 Date: 2013-11-27 prognosticroc Package License: GPL (>=2) LazyLoad: yes AggregatedPROC IndividualPROC Compute prognostic ROC curve based on survival function already determined by the user (parametric model, Kaplan-Meier curve, weighted estimations,...) Compute prognostic ROC curve based on individual data, survival function are determined by the Kaplan-Meier estimator, confidence intervals are obtained by bootstrap Author(s) Y. Foucher <Yohann.Foucher@univ-nantes.fr> and C. Combescure <Christophe.Combescure@hcuge.ch> References Combescure C, Perneger TV, Weber DC, Daures JP and Foucher Y. Prognostic ROC curves: a method for representing the overall discriminative capacity of binary markers with right-censored time-to-event endpoints. Manuscript in press. Epidemiology. 2013. See Also URL: http://www.divat.fr

AggregatedPROC 3 AggregatedPROC Prognostic ROC curve based on survival probabilities already computed Description The user enters the survival according to the model she/he chooses. The area under the prognostic ROC curve is assessed by using the trapezoidal rules. The extrapolated areas (when survival curves do not reach 0) are performed by assuming pessimist, optimist and non-informative situation. Usage AggregatedPROC(Time.LR, Surv.LR, Time.HR, Surv.HR) Arguments Time.LR Surv.LR Time.HR Surv.HR A numeric vector with the survival times in the low risk group. A numeric vector with the survival probabilities corresponding to Time.LR A numeric vector with the survival times in the high risk group. A numeric vector with the survival probabilities corresponding to Time.HR. Details The maximum prognostic time is the minimum between the maximum of Time.LR and the maximum of Time.HR. Value max.time table auc This is the maximum prognostic time used for the analysis This data frame presents the different time cut-offs associated with the coordinates of the ROC curves. This data frame presents the different estimations of the area under the prognostic ROC curve: the lower bound, the pessimist, the non-informative, the optimist and the upper bound. Author(s) Y. Foucher <Yohann.Foucher@univ-nantes.fr> and C. Combescure <Christophe.Combescure@hcuge.ch> References Combescure C, Perneger TV, Weber DC, Daures JP and Foucher Y. Prognostic ROC curves: a method for representing the overall discriminative capacity of binary markers with right-censored time-to-event endpoints. Manuscript in press. Epidemiology. 2013.

4 IndividualPROC Examples # example of two survival curves using exponential distributions time.hr <- seq(0, 600, by=5) time.lr <- seq(0, 500, by=2) surv.hr <- exp(-0.005*time.hr) surv.lr <- exp(-0.003*time.lr) # Illustration of both survival curves plot(time.hr, surv.hr, xlab="time (in days)", ylab="patient survival", lwd=2, type="l") lines(time.lr, surv.lr, lty=2, col=2, lwd=2) legend("topright", c("high-risk Group", "Low-Risk Group"), lwd=2, col=1:2, lty=1:2) # Computation of the prognostic ROC curve proc.result <- AggregatedPROC(time.lr, surv.lr, time.hr, surv.hr) # Representation of the prognostic ROC curve plot(proc.result$table$x, proc.result$table$y, type="l", lwd=2, xlim=c(0,1), ylim=c(0,1), xlab="1-survival in the low risk group", ylab="1-survival in the high risk group") abline(c(0,0), c(1,1), lty=2) # The pessimist value of the area under the curve proc.result$auc$pessimist IndividualPROC Prognostic ROC curve based on individual data Description Usage The user enters individual survival data. The area under the prognostic ROC curve is assessed by using the trapezoidal rules. The extrapolated areas (when survival curves do not reach 0) are performed by assuming pessimist, optimist and non-informative situation. The confidence intervals are obtained by non-parametric bootstrapping. IndividualPROC(times, failures, variable, B) Arguments times failures variable A numeric vector with the follow up times. A numeric vector with the event indicator (0=right censored, 1=event). A numeric vector with the result of the binary test (only two groups). The variable equals 1 for the high risk group and 0 for the low risk group.

IndividualPROC 5 B The number of bootstrap samples to compute the confidence intervals. The default value is 0, which corresponds to no confidence interval computation. Details Value The maximum prognostic time is the minimum between the two last observed times of failure in both groups. max.time table auc CI.95 auc.boot This is the maximum prognostic time used for the analysis This data frame presents the different time cut-offs associated with the coordinates of the ROC curves. This data frame presents the different estimations of the area under the prognostic ROC curve: the lower bound, the pessimist, the non-informative, the optimist and the upper bound. This data frame presents the 95 percentage confidence intervals of the area under the prognostic ROC curve: the lower bound, the pessimist, the non-informative, the optimist and the upper bound. This data frame presents the different estimations of the area under the prognostic ROC curve for each of the B bootstrap samples: the lower bound, the pessimist, the non-informative, the optimist and the upper bound. Author(s) Y. Foucher <Yohann.Foucher@univ-nantes.fr> and C. Combescure <Christophe.Combescure@hcuge.ch> References Combescure C, Perneger TV, Weber DC, Daures JP and Foucher Y. Prognostic ROC curves: a method for representing the overall discriminative capacity of binary markers with right-censored time-to-event endpoints. Manuscript in press. Epidemiology. 2013. Examples ################################################################### # example of two samples with different exponential distributions # ################################################################### n1 <- 200 n2 <- 200 grp <- c(rep(1, n1), rep(0, n2)) time.evt <- c(rexp(n1, rate = 1.2), rexp(n2, rate = 0.5)) time.cen <- rexp(n1+n2, rate = 0.2) time <- pmin(time.evt, time.cen) evt <- 1*(time.evt < time.cen)

6 IndividualPROC # Illustration of both survival curves surv.temp <- survfit(surv(time, evt) ~ grp) plot(surv.temp, lty = 2:3) # Computation of the prognostic ROC curve proc.result <- IndividualPROC(time, evt, grp, B=50) # Use B>50 for real applications # Representation of the prognostic ROC curve plot(proc.result$table$x, proc.result$table$y, type="l", lwd=2, xlim=c(0,1), ylim=c(0,1), xlab="1-survival in the low risk group", ylab="1-survival in the high risk group") abline(c(0,0), c(1,1), lty=2) # The corresponding 95% CI of the pessimist value proc.result$ci.95$pessimist

Index Topic Individual data Topic Kaplan and Meier Topic Prognostic ROC AggregatedPROC, 3 prognosticroc-package, 2 Topic Survival AggregatedPROC, 3 prognosticroc-package, 2 AggregatedPROC, 3 prognosticroc (prognosticroc-package), 2 prognosticroc-package, 2 7