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      There is no such thing as a validated prediction model

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          Abstract

          Background

          Clinical prediction models should be validated before implementation in clinical practice. But is favorable performance at internal validation or one external validation sufficient to claim that a prediction model works well in the intended clinical context?

          Main body

          We argue to the contrary because (1) patient populations vary, (2) measurement procedures vary, and (3) populations and measurements change over time. Hence, we have to expect heterogeneity in model performance between locations and settings, and across time. It follows that prediction models are never truly validated. This does not imply that validation is not important. Rather, the current focus on developing new models should shift to a focus on more extensive, well-conducted, and well-reported validation studies of promising models.

          Conclusion

          Principled validation strategies are needed to understand and quantify heterogeneity, monitor performance over time, and update prediction models when appropriate. Such strategies will help to ensure that prediction models stay up-to-date and safe to support clinical decision-making.

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          Most cited references57

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          Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD): Explanation and Elaboration

          The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) Statement includes a 22-item checklist, which aims to improve the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. This explanation and elaboration document describes the rationale; clarifies the meaning of each item; and discusses why transparent reporting is important, with a view to assessing risk of bias and clinical usefulness of the prediction model. Each checklist item of the TRIPOD Statement is explained in detail and accompanied by published examples of good reporting. The document also provides a valuable reference of issues to consider when designing, conducting, and analyzing prediction model studies. To aid the editorial process and help peer reviewers and, ultimately, readers and systematic reviewers of prediction model studies, it is recommended that authors include a completed checklist in their submission. The TRIPOD checklist can also be downloaded from www.tripod-statement.org.
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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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              Calibration: the Achilles heel of predictive analytics

              Background The assessment of calibration performance of risk prediction models based on regression or more flexible machine learning algorithms receives little attention. Main text Herein, we argue that this needs to change immediately because poorly calibrated algorithms can be misleading and potentially harmful for clinical decision-making. We summarize how to avoid poor calibration at algorithm development and how to assess calibration at algorithm validation, emphasizing balance between model complexity and the available sample size. At external validation, calibration curves require sufficiently large samples. Algorithm updating should be considered for appropriate support of clinical practice. Conclusion Efforts are required to avoid poor calibration when developing prediction models, to evaluate calibration when validating models, and to update models when indicated. The ultimate aim is to optimize the utility of predictive analytics for shared decision-making and patient counseling.
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                Author and article information

                Contributors
                M.vanSmeden@umcutrecht.nl
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                24 February 2023
                24 February 2023
                2023
                : 21
                : 70
                Affiliations
                [1 ]GRID grid.5596.f, ISNI 0000 0001 0668 7884, Department of Development and Regeneration, , KU Leuven, ; Leuven, Belgium
                [2 ]GRID grid.5596.f, ISNI 0000 0001 0668 7884, EPI-Center, KU Leuven, ; Leuven, Belgium
                [3 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Biomedical Data Sciences, , Leiden University Medical Center, ; Leiden, Netherlands
                [4 ]GRID grid.5012.6, ISNI 0000 0001 0481 6099, Department of Epidemiology, , CAPHRI Care and Public Health Research Institute, Maastricht University, ; Maastricht, Netherlands
                [5 ]GRID grid.5477.1, ISNI 0000000120346234, Julius Center for Health Sciences and Primary Care, , University Medical Center Utrecht, Utrecht University, ; Universiteitsweg 100, 3584 CG Utrecht, Netherlands
                Author information
                http://orcid.org/0000-0003-1613-7450
                http://orcid.org/0000-0002-7787-0122
                http://orcid.org/0000-0002-3037-122X
                http://orcid.org/0000-0002-5529-1541
                Article
                2779
                10.1186/s12916-023-02779-w
                9951847
                36829188
                d258ea47-a216-47f1-a509-0b446a1cfa19
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 13 October 2022
                : 10 February 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003130, Fonds Wetenschappelijk Onderzoek;
                Award ID: G097322N
                Award Recipient :
                Categories
                Opinion
                Custom metadata
                © The Author(s) 2023

                Medicine
                risk prediction models,predictive analytics,internal validation,external validation,heterogeneity,model performance,calibration,discrimination

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