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Quantifying and Interpreting the Prediction Accuracy of Models for the Time of a Cardiovascular Event—Moving Beyond C StatisticA Review

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Importance  For personalized or stratified medicine, it is critical to establish a reliable and efficient prediction model for a clinical outcome of interest. The goal is to develop a parsimonious model with fewer predictors for broad future application without compromising predictability. A general approach is to construct various empirical models via individual patients’ specific baseline characteristics/biomarkers and then evaluate their relative merits. When the outcome of interest is the timing of a cardiovascular event, a commonly used metric to assess the adequacy of the fitted models is based on C statistics. These measures quantify a model’s ability to separate those who develop events earlier from those who develop them later or not at all (discrimination), but they do not measure how closely model estimates match observed outcomes (prediction accuracy). Metrics that provide clinically interpretable measures to quantify prediction accuracy are needed.

Observations  C statistics measure the concordance between the risk scores derived from the model and the observed event time observations. However, C statistics do not quantify the model prediction accuracy. The integrated Brier Score, which calculates the mean squared distance between the empirical cumulative event-free curve and its individual patient’s counterparts, estimates the prediction accuracy, but it is not clinically intuitive. A simple alternative measure is the average distance between the observed and predicted event times over the entire study population. This metric directly quantifies the model prediction accuracy and has often been used to evaluate the goodness of fit of the assumed models in settings other than survival data. This time-scale measure is easier to interpret than the C statistics or the Brier score.

Conclusions and Relevance  This article enhances our understanding of the model selection/evaluation process with respect to prediction accuracy. A simple, intuitive measure for quantifying such accuracy beyond C statistics can improve the reliability and efficiency of the selected model for personalized and stratified medicine.

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Article Information

Accepted for Publication: December 1, 2022.

Published Online: February 1, 2023. doi:10.1001/jamacardio.2022.5279

Corresponding Author: Lee-Jen Wei, PhD, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, 655 Huntington Ave, Boston, MA 02115 (wei@hsph.harvard.edu).

Author Contributions: Drs Wang and Claggett had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Wang and Claggett contributed equally as co–first authors.

Concept and design: Wang, Claggett, Tian, Pfeffer, Wei.

Acquisition, analysis, or interpretation of data: Wang, Claggett, Malachias, Wei.

Drafting of the manuscript: Wang, Claggett, Tian, Wei.

Critical revision of the manuscript for important intellectual content: Wang, Claggett, Malachias, Pfeffer, Wei.

Statistical analysis: Wang, Claggett, Tian, Malachias, Wei.

Administrative, technical, or material support: Wang, Wei.

Supervision: Wei.

Conflict of Interest Disclosures: Dr Claggett reported receiving consulting fees from Cardurion, Corvia, and Novartis outside the submitted work. Dr Malachias reported receiving lecture fees from Bayer, Boehringer Ingelheim, Novo Nordisk, Daiichi-Sankyo, Novartis, and Libbs outside the submitted work. Dr Pfeffer reported receiving grants from Novartis; personal fees from Alnylam, AstraZeneca, Boehringer Ingelheim, Eli Lilly Alliance, Corvidia, DalCor, GlaxoSmithKline, Lexicon, the National Heart, Lung, and Blood Institute’s Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS), Novartis, Novo Nordisk, Peerbridge, and Sanofi; and stock options from DalCor outside the submitted work. Dr Wei did not receive consulting fees for this research project. No other disclosures were reported.

Funding/Support: This research was partially supported by grant R01HL089778 from the US National Institutes of Health (Dr Tian).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Robert O. Bonow, MD, Editor, JAMA Cardiology, and Michael J. Pencina, PhD, Deputy Editor for Statistics, JAMA Cardiology, and reviewers for their insightful, extensive comments/suggestions on the manuscript. No one was financially compensated for their contribution.

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