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      Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers

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          Abstract

          Background

          Decision curve analysis is a novel method for evaluating diagnostic tests, prediction models and molecular markers. It combines the mathematical simplicity of accuracy measures, such as sensitivity and specificity, with the clinical applicability of decision analytic approaches. Most critically, decision curve analysis can be applied directly to a data set, and does not require the sort of external data on costs, benefits and preferences typically required by traditional decision analytic techniques.

          Methods

          In this paper we present several extensions to decision curve analysis including correction for overfit, confidence intervals, application to censored data (including competing risk) and calculation of decision curves directly from predicted probabilities. All of these extensions are based on straightforward methods that have previously been described in the literature for application to analogous statistical techniques.

          Results

          Simulation studies showed that repeated 10-fold crossvalidation provided the best method for correcting a decision curve for overfit. The method for applying decision curves to censored data had little bias and coverage was excellent; for competing risk, decision curves were appropriately affected by the incidence of the competing risk and the association between the competing risk and the predictor of interest. Calculation of decision curves directly from predicted probabilities led to a smoothing of the decision curve.

          Conclusion

          Decision curve analysis can be easily extended to many of the applications common to performance measures for prediction models. Software to implement decision curve analysis is provided.

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          Most cited references11

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          Time-dependent ROC curves for censored survival data and a diagnostic marker.

          ROC curves are a popular method for displaying sensitivity and specificity of a continuous diagnostic marker, X, for a binary disease variable, D. However, many disease outcomes are time dependent, D(t), and ROC curves that vary as a function of time may be more appropriate. A common example of a time-dependent variable is vital status, where D(t) = 1 if a patient has died prior to time t and zero otherwise. We propose summarizing the discrimination potential of a marker X, measured at baseline (t = 0), by calculating ROC curves for cumulative disease or death incidence by time t, which we denote as ROC(t). A typical complexity with survival data is that observations may be censored. Two ROC curve estimators are proposed that can accommodate censored data. A simple estimator is based on using the Kaplan-Meier estimator for each possible subset X > c. However, this estimator does not guarantee the necessary condition that sensitivity and specificity are monotone in X. An alternative estimator that does guarantee monotonicity is based on a nearest neighbor estimator for the bivariate distribution function of (X, T), where T represents survival time (Akritas, M. J., 1994, Annals of Statistics 22, 1299-1327). We present an example where ROC(t) is used to compare a standard and a modified flow cytometry measurement for predicting survival after detection of breast cancer and an example where the ROC(t) curve displays the impact of modifying eligibility criteria for sample size and power in HIV prevention trials.
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            Internal validation of predictive models: efficiency of some procedures for logistic regression analysis.

            The performance of a predictive model is overestimated when simply determined on the sample of subjects that was used to construct the model. Several internal validation methods are available that aim to provide a more accurate estimate of model performance in new subjects. We evaluated several variants of split-sample, cross-validation and bootstrapping methods with a logistic regression model that included eight predictors for 30-day mortality after an acute myocardial infarction. Random samples with a size between n = 572 and n = 9165 were drawn from a large data set (GUSTO-I; n = 40,830; 2851 deaths) to reflect modeling in data sets with between 5 and 80 events per variable. Independent performance was determined on the remaining subjects. Performance measures included discriminative ability, calibration and overall accuracy. We found that split-sample analyses gave overly pessimistic estimates of performance, with large variability. Cross-validation on 10% of the sample had low bias and low variability, but was not suitable for all performance measures. Internal validity could best be estimated with bootstrapping, which provided stable estimates with low bias. We conclude that split-sample validation is inefficient, and recommend bootstrapping for estimation of internal validity of a predictive logistic regression model.
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              Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer.

              Radical cystectomy and pelvic lymphadenectomy (PLND) remains the standard treatment for localized and regionally advanced invasive bladder cancers. We have constructed an international bladder cancer database from centers of excellence in the management of bladder cancer consisting of patients treated with radical cystectomy and PLND. The goal of this study was the development of a prognostic outcomes nomogram to predict the 5-year disease recurrence risk after radical cystectomy. Institutional radical cystectomy databases containing detailed information on bladder cancer patients were obtained from 12 centers of excellence worldwide. Data were collected on more than 9,000 postoperative patients and combined into a relational database formatted with patient characteristics, pathologic details of the pre- and postcystectomy specimens, and recurrence and survival status. Patients with available information for all selected study criteria were included in the formation of the final prognostic nomogram designed to predict 5-year progression-free probability. The final nomogram included information on patient age, sex, time from diagnosis to surgery, pathologic tumor stage and grade, tumor histologic subtype, and regional lymph node status. The predictive accuracy of the constructed international nomogram (concordance index, 0.75) was significantly better than standard American Joint Committee on Cancer TNM (concordance index, 0.68; P < .001) or standard pathologic subgroupings (concordance index, 0.62; P < .001). We have developed an international bladder cancer nomogram predicting recurrence risk after radical cystectomy for bladder cancer. The nomogram outperformed prognostic models that use standard pathologic subgroupings and should improve our ability to provide accurate risk assessments to patients after the surgical management of bladder cancer.
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                Author and article information

                Journal
                BMC Med Inform Decis Mak
                BMC Medical Informatics and Decision Making
                BioMed Central
                1472-6947
                2008
                26 November 2008
                : 8
                : 53
                Affiliations
                [1 ]Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 East 63 rd Street, New York, NY 10065, USA
                Article
                1472-6947-8-53
                10.1186/1472-6947-8-53
                2611975
                19036144
                b39718ef-61bd-4a39-84b3-89a8132b25a4
                Copyright © 2008 Vickers et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 June 2008
                : 26 November 2008
                Categories
                Technical Advance

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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