Clinical Prediction Models

The second edition of this volume provides insight and practical illustrations on how modern statistical concepts and regression methods can be applied in medical prediction problems, including diagnostic and prognostic outcomes. Many advances have been made in statistical approaches towards outcome prediction, but a sensible strategy is needed for model development, validation, and updating, such that prediction models can better support medical practice. There is an increasing need for personalized evidence-based medicine that uses an individualized approach to medical decision-making. In this Big Data era, there is expanded access to large volumes of routinely collected data and an increased number of applications for prediction models, such as targeted early detection of disease and individualized approaches to diagnostic testing and treatment. Clinical Prediction Models presents a practical checklist that needs to be considered for development of a valid prediction model. Steps include preliminary considerations such as dealing with missing values; coding of predictors; selection of main effects and interactions for a multivariable model; estimation of model parameters with shrinkage methods and incorporation of external data; evaluation of performance and usefulness; internal validation; and presentation formatting. The text also addresses common issues that make prediction models suboptimal, such as small sample sizes, exaggerated claims, and poor generalizability. The text is primarily intended for clinical epidemiologists and biostatisticians. Including many case studies and publicly available R code and data sets, the book is also appropriate as a textbook for a graduate course on predictive modeling in diagnosis and prognosis. While practical in nature, the book also provides a philosophical perspective on data analysis in medicine that goes beyond predictive modeling. Updates to this new and expanded edition include: • A discussion of Big Data and its implications for the design of prediction models • Machine learning issues • More simulations with missing ‘y’ values • Extended discussion on between-cohort heterogeneity • Description of ShinyApp • Updated LASSO illustration • New case studies

Prediction models are important in various fields, including medicine, physics, meteorology, and finance. Prediction models will become more relevant in the medical field with the increase in knowledge on potential predictors of outcome, e.g. from genetics. Also, the number of applications will increase, e.g. with targeted early detection of disease, and individualized approaches to diagnostic testing and treatment. The current era of evidence-based medicine asks for an individualized approach to medical decision-making. Evidence-based medicine has a central place for meta-analysis to summarize results from randomized controlled trials; similarly prediction models may summarize the effects of predictors to provide individu- ized predictions of a diagnostic or prognostic outcome. Why Read This Book? My motivation for working on this book stems primarily from the fact that the development and applications of prediction models are often suboptimal in medical publications. With this book I hope to contribute to better understanding of relevant issues and give practical advice on better modelling strategies than are nowadays widely used. Issues include: (a) Better predictive modelling is sometimes easily possible; e.g. a large data set with high quality data is available, but all continuous predictors are dich- omized, which is known to have several disadvantages.

The second edition of this volume provides insight and practical illustrations on how modern statistical concepts and regression methods can be applied in medical prediction problems, including diagnostic and prognostic outcomes. Many advances have been made in statistical approaches towards outcome prediction, but a sensible strategy is needed for model development, validation, and updating, such that prediction models can better support medical practice. There is an increasing need for personalized evidence-based medicine that uses an individualized approach to medical decision-making. In this Big Data era, there is expanded access to large volumes of routinely collected data and an increased number of applications for prediction models, such as targeted early detection of disease and individualized approaches to diagnostic testing and treatment. Clinical Prediction Models presents a practical checklist that needs to be considered for development of a valid prediction model. Steps include preliminary considerations such as dealing with missing values; coding of predictors; selection of main effects and interactions for a multivariable model; estimation of model parameters with shrinkage methods and incorporation of external data; evaluation of performance and usefulness; internal validation; and presentation formatting. The text also addresses common issues that make prediction models suboptimal, such as small sample sizes, exaggerated claims, and poor generalizability. The text is primarily intended for clinical epidemiologists and biostatisticians. Including many case studies and publicly available R code and data sets, the book is also appropriate as a textbook for a graduate course on predictive modeling in diagnosis and prognosis. While practical in nature, the book also provides a philosophical perspective on data analysis in medicine that goes beyond predictive modeling. Updates to this new and expanded edition include: • A discussion of Big Data and its implications for the design of prediction models • Machine learning issues • More simulations with missing ‘y’ values • Extended discussion on between-cohort heterogeneity • Description of ShinyApp • Updated LASSO illustration • New case studies

This open access book comprehensively covers the fundamentals of clinical data science, focusing on data collection, modelling and clinical applications. Topics covered in the first section on data collection include: data sources, data at scale (big data), data stewardship (FAIR data) and related privacy concerns. Aspects of predictive modelling using techniques such as classification, regression or clustering, and prediction model validation will be covered in the second section. The third section covers aspects of (mobile) clinical decision support systems, operational excellence and value-based healthcare. Fundamentals of Clinical Data Science is an essential resource for healthcare professionals and IT consultants intending to develop and refine their skills in personalized medicine, using solutions based on large datasets from electronic health records or telemonitoring programmes. The book’s promise is “no math, no code”and will explain the topics in a style that is optimized for a healthcare audience.

Medical Risk Prediction Models: With Ties to Machine Learning is a hands-on book for clinicians, epidemiologists, and professional statisticians who need to make or evaluate a statistical prediction model based on data. The subject of the book is the patient’s individualized probability of a medical event within a given time horizon. Gerds and Kattan describe the mathematical details of making and evaluating a statistical prediction model in a highly pedagogical manner while avoiding mathematical notation. Read this book when you are in doubt about whether a Cox regression model predicts better than a random survival forest. Features: All you need to know to correctly make an online risk calculator from scratch Discrimination, calibration, and predictive performance with censored data and competing risks R-code and illustrative examples Interpretation of prediction performance via benchmarks Comparison and combination of rival modeling strategies via cross-validation Thomas A. Gerds is a professor at the Biostatistics Unit at the University of Copenhagen and is affiliated with the Danish Heart Foundation. He is the author of several R-packages on CRAN and has taught statistics courses to non-statisticians for many years. Michael W. Kattan is a highly cited author and Chair of the Department of Quantitative Health Sciences at Cleveland Clinic. He is a Fellow of the American Statistical Association and has received two awards from the Society for Medical Decision Making: the Eugene L. Saenger Award for Distinguished Service, and the John M. Eisenberg Award for Practical Application of Medical Decision-Making Research.

"What is going to happen to me?" Most patients ask this question during a clinical encounter with a health professional. As well as learning what problem they have (diagnosis) and what needs to be done about it (treatment), patients want to know about their future health and wellbeing (prognosis). Prognosis research can provide answers to this question and satisfy the need for individuals to understand the possible outcomes of their condition, with and without treatment. Central to modern medical practise, the topic of prognosis is the basis of decision making in healthcare and policy development. It translates basic and clinical science into practical care for patients and populations. Prognosis Research in Healthcare: Concepts, Methods and Impact provides a comprehensive overview of the field of prognosis and prognosis research and gives a global perspective on how prognosis research and prognostic information can improve the outcomes of healthcare. It details how to design, carry out, analyse and report prognosis studies, and how prognostic information can be the basis for tailored, personalised healthcare. In particular, the book discusses how information about the characteristics of people, their health, and environment can be used to predict an individual's future health. Prognosis Research in Healthcare: Concepts, Methods and Impact, addresses all types of prognosis research and provides a practical step-by-step guide to undertaking and interpreting prognosis research studies, ideal for medical students, health researchers, healthcare professionals and methodologists, as well as for guideline and policy makers in healthcare wishing to learn more about the field of prognosis.

Applied Predictive Modeling covers the overall predictive modeling process, beginning with the crucial steps of data preprocessing, data splitting and foundations of model tuning. The text then provides intuitive explanations of numerous common and modern regression and classification techniques, always with an emphasis on illustrating and solving real data problems. The text illustrates all parts of the modeling process through many hands-on, real-life examples, and every chapter contains extensive R code for each step of the process. This multi-purpose text can be used as an introduction to predictive models and the overall modeling process, a practitioner’s reference handbook, or as a text for advanced undergraduate or graduate level predictive modeling courses. To that end, each chapter contains problem sets to help solidify the covered concepts and uses data available in the book’s R package. This text is intended for a broad audience as both an introduction to predictive models as well as a guide to applying them. Non-mathematical readers will appreciate the intuitive explanations of the techniques while an emphasis on problem-solving with real data across a wide variety of applications will aid practitioners who wish to extend their expertise. Readers should have knowledge of basic statistical ideas, such as correlation and linear regression analysis. While the text is biased against complex equations, a mathematical background is needed for advanced topics.

There is a huge amount of literature on statistical models for the prediction of survival after diagnosis of a wide range of diseases like cancer, cardiovascular disease, and chronic kidney disease. Current practice is to use prediction models based on the Cox proportional hazards model and to present those as static models for remaining lifetime a

This open access book explores ways to leverage information technology and machine learning to combat disease and promote health, especially in resource-constrained settings. It focuses on digital disease surveillance through the application of machine learning to non-traditional data sources. Developing countries are uniquely prone to large-scale emerging infectious disease outbreaks due to disruption of ecosystems, civil unrest, and poor healthcare infrastructure – and without comprehensive surveillance, delays in outbreak identification, resource deployment, and case management can be catastrophic. In combination with context-informed analytics, students will learn how non-traditional digital disease data sources – including news media, social media, Google Trends, and Google Street View – can fill critical knowledge gaps and help inform on-the-ground decision-making when formal surveillance systems are insufficient.

Individual Participant Data Meta-Analysis: A Handbook for Healthcare Research provides a comprehensive introduction to the fundamental principles and methods that healthcare researchers need when considering, conducting or using individual participant data (IPD) meta-analysis projects. Written and edited by researchers with substantial experience in the field, the book details key concepts and practical guidance for each stage of an IPD meta-analysis project, alongside illustrated examples and summary learning points. Split into five parts, the book chapters take the reader through the journey from initiating and planning IPD projects to obtaining, checking, and meta-analysing IPD, and appraising and reporting findings. The book initially focuses on the synthesis of IPD from randomised trials to evaluate treatment effects, including the evaluation of participant-level effect modifiers (treatment-covariate interactions). Detailed extension is then made to specialist topics such as diagnostic test accuracy, prognostic factors, risk prediction models, and advanced statistical topics such as multivariate and network meta-analysis, power calculations, and missing data. Intended for a broad audience, the book will enable the reader to: Understand the advantages of the IPD approach and decide when it is needed over a conventional systematic review Recognise the scope, resources and challenges of IPD meta-analysis projects Appreciate the importance of a multi-disciplinary project team and close collaboration with the original study investigators Understand how to obtain, check, manage and harmonise IPD from multiple studies Examine risk of bias (quality) of IPD and minimise potential biases throughout the project Understand fundamental statistical methods for IPD meta-analysis, including two-stage and one-stage approaches (and their differences), and statistical software to implement them Clearly report and disseminate IPD meta-analyses to inform policy, practice and future research Critically appraise existing IPD meta-analysis projects Address specialist topics such as effect modification, multiple correlated outcomes, multiple treatment comparisons, non-linear relationships, test accuracy at multiple thresholds, multiple imputation, and developing and validating clinical prediction models Detailed examples and case studies are provided throughout.