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 epidemiology


Can synthetic data reproduce real-world findings in epidemiology? A replication study using tree-based generative AI

Kapar, Jan, Günther, Kathrin, Vallis, Lori Ann, Berger, Klaus, Binder, Nadine, Brenner, Hermann, Castell, Stefanie, Fischer, Beate, Harth, Volker, Holleczek, Bernd, Intemann, Timm, Ittermann, Till, Karch, André, Keil, Thomas, Krist, Lilian, Lange, Berit, Leitzmann, Michael F., Nimptsch, Katharina, Obi, Nadia, Pigeot, Iris, Pischon, Tobias, Schikowski, Tamara, Schmidt, Börge, Schmidt, Carsten Oliver, Sedlmair, Anja M., Tanoey, Justine, Wienbergen, Harm, Wienke, Andreas, Wigmann, Claudia, Wright, Marvin N.

arXiv.org Machine Learning

Generative artificial intelligence for synthetic data generation holds substantial potential to address practical challenges in epidemiology. However, many current methods suffer from limited quality, high computational demands, and complexity for non-experts. Furthermore, common evaluation strategies for synthetic data often fail to directly reflect statistical utility. Against this background, a critical underexplored question is whether synthetic data can reliably reproduce key findings from epidemiological research. We propose the use of adversarial random forests (ARF) as an efficient and convenient method for synthesizing tabular epidemiological data. To evaluate its performance, we replicated statistical analyses from six epidemiological publications and compared original with synthetic results. These publications cover blood pressure, anthropometry, myocardial infarction, accelerometry, loneliness, and diabetes, based on data from the German National Cohort (NAKO Gesundheitsstudie), the Bremen STEMI Registry U45 Study, and the Guelph Family Health Study. Additionally, we assessed the impact of dimensionality and variable complexity on synthesis quality by limiting datasets to variables relevant for individual analyses, including necessary derivations. Across all replicated original studies, results from multiple synthetic data replications consistently aligned with original findings. Even for datasets with relatively low sample size-to-dimensionality ratios, the replication outcomes closely matched the original results across various descriptive and inferential analyses. Reducing dimensionality and pre-deriving variables further enhanced both quality and stability of the results.


Why can't Epidemiology be automated (yet)?

Bann, David, Lowther, Ed, Wright, Liam, Kovalchuk, Yevgeniya

arXiv.org Artificial Intelligence

Recent advances in artificial intelligence (AI) - particularly generative AI - present new opportunities to accelerate, or even automate, epidemiological research. Unlike disciplines based on physical experimentation, a sizable fraction of Epidemiology relies on secondary data analysis and thus is well-suited for such augmentation. Yet, it remains unclear which specific tasks can benefit from AI interventions or where roadblocks exist. Awareness of current AI capabilities is also mixed. Here, we map the landscape of epidemiological tasks using existing datasets - from literature review to data access, analysis, writing up, and dissemination - and identify where existing AI tools offer efficiency gains. While AI can increase productivity in some areas such as coding and administrative tasks, its utility is constrained by limitations of existing AI models (e.g. hallucinations in literature reviews) and human systems (e.g. barriers to accessing datasets). Through examples of AI-generated epidemiological outputs, including fully AI-generated papers, we demonstrate that recently developed agentic systems can now design and execute epidemiological analysis, albeit to varied quality (see https://github.com/edlowther/automated-epidemiology). Epidemiologists have new opportunities to empirically test and benchmark AI systems; realising the potential of AI will require two-way engagement between epidemiologists and engineers.


Performance of Cross-Validated Targeted Maximum Likelihood Estimation

Smith, Matthew J., Phillips, Rachael V., Maringe, Camille, Luque-Fernandez, Miguel Angel

arXiv.org Machine Learning

Background: Advanced methods for causal inference, such as targeted maximum likelihood estimation (TMLE), require certain conditions for statistical inference. However, in situations where there is not differentiability due to data sparsity or near-positivity violations, the Donsker class condition is violated. In such situations, TMLE variance can suffer from inflation of the type I error and poor coverage, leading to conservative confidence intervals. Cross-validation of the TMLE algorithm (CVTMLE) has been suggested to improve on performance compared to TMLE in settings of positivity or Donsker class violations. We aim to investigate the performance of CVTMLE compared to TMLE in various settings. Methods: We utilised the data-generating mechanism as described in Leger et al. (2022) to run a Monte Carlo experiment under different Donsker class violations. Then, we evaluated the respective statistical performances of TMLE and CVTMLE with different super learner libraries, with and without regression tree methods. Results: We found that CVTMLE vastly improves confidence interval coverage without adversely affecting bias, particularly in settings with small sample sizes and near-positivity violations. Furthermore, incorporating regression trees using standard TMLE with ensemble super learner-based initial estimates increases bias and variance leading to invalid statistical inference. Conclusions: It has been shown that when using CVTMLE the Donsker class condition is no longer necessary to obtain valid statistical inference when using regression trees and under either data sparsity or near-positivity violations. We show through simulations that CVTMLE is much less sensitive to the choice of the super learner library and thereby provides better estimation and inference in cases where the super learner library uses more flexible candidates and is prone to overfitting.


High-dimensional multiple imputation (HDMI) for partially observed confounders including natural language processing-derived auxiliary covariates

Weberpals, Janick, Shaw, Pamela A., Lin, Kueiyu Joshua, Wyss, Richard, Plasek, Joseph M, Zhou, Li, Ngan, Kerry, DeRamus, Thomas, Raman, Sudha R., Hammill, Bradley G., Lee, Hana, Toh, Sengwee, Connolly, John G., Dandreo, Kimberly J., Tian, Fang, Liu, Wei, Li, Jie, Hernández-Muñoz, José J., Schneeweiss, Sebastian, Desai, Rishi J.

arXiv.org Artificial Intelligence

Multiple imputation (MI) models can be improved by including auxiliary covariates (AC), but their performance in high-dimensional data is not well understood. We aimed to develop and compare high-dimensional MI (HDMI) approaches using structured and natural language processing (NLP)-derived AC in studies with partially observed confounders. We conducted a plasmode simulation study using data from opioid vs. non-steroidal anti-inflammatory drug (NSAID) initiators (X) with observed serum creatinine labs (Z2) and time-to-acute kidney injury as outcome. We simulated 100 cohorts with a null treatment effect, including X, Z2, atrial fibrillation (U), and 13 other investigator-derived confounders (Z1) in the outcome generation. We then imposed missingness (MZ2) on 50% of Z2 measurements as a function of Z2 and U and created different HDMI candidate AC using structured and NLP-derived features. We mimicked scenarios where U was unobserved by omitting it from all AC candidate sets. Using LASSO, we data-adaptively selected HDMI covariates associated with Z2 and MZ2 for MI, and with U to include in propensity score models. The treatment effect was estimated following propensity score matching in MI datasets and we benchmarked HDMI approaches against a baseline imputation and complete case analysis with Z1 only. HDMI using claims data showed the lowest bias (0.072). Combining claims and sentence embeddings led to an improvement in the efficiency displaying the lowest root-mean-squared-error (0.173) and coverage (94%). NLP-derived AC alone did not perform better than baseline MI. HDMI approaches may decrease bias in studies with partially observed confounders where missingness depends on unobserved factors.


A Review of Graph Neural Networks in Epidemic Modeling

Liu, Zewen, Wan, Guancheng, Prakash, B. Aditya, Lau, Max S. Y., Jin, Wei

arXiv.org Artificial Intelligence

Since the onset of the COVID-19 pandemic, there has been a growing interest in studying epidemiological models. Traditional mechanistic models mathematically describe the transmission mechanisms of infectious diseases. However, they often suffer from limitations of oversimplified or fixed assumptions, which could cause sub-optimal predictive power and inefficiency in capturing complex relation information. Consequently, Graph Neural Networks (GNNs) have emerged as a progressively popular tool in epidemic research. In this paper, we endeavor to furnish a comprehensive review of GNNs in epidemic tasks and highlight potential future directions. To accomplish this objective, we introduce hierarchical taxonomies for both epidemic tasks and methodologies, offering a trajectory of development within this domain. For epidemic tasks, we establish a taxonomy akin to those typically employed within the epidemic domain. For methodology, we categorize existing work into Neural Models and Hybrid Models. Following this, we perform an exhaustive and systematic examination of the methodologies, encompassing both the tasks and their technical details. Furthermore, we discuss the limitations of existing methods from diverse perspectives and systematically propose future research directions. This survey aims to bridge literature gaps and promote the progression of this promising field, with a list of relevant papers at https://github.com/Emory-Melody/awesome-epidemic-modelingpapers. We hope that it will facilitate synergies between the communities of GNNs and epidemiology, and contribute to their collective progress.


Creating a Discipline-specific Commons for Infectious Disease Epidemiology

Wagner, Michael M., Hogan, William, Levander, John, Darr, Adam, Diller, Matt, Sibilla, Max, Sperringer,, Alexander T. Loiacono. Terence Jr., Brown, Shawn T.

arXiv.org Artificial Intelligence

Objective: To create a commons for infectious disease (ID) epidemiology in which epidemiologists, public health officers, data producers, and software developers can not only share data and software, but receive assistance in improving their interoperability. Materials and Methods: We represented 586 datasets, 54 software, and 24 data formats in OWL 2 and then used logical queries to infer potentially interoperable combinations of software and datasets, as well as statistics about the FAIRness of the collection. We represented the objects in DATS 2.2 and a software metadata schema of our own design. We used these representations as the basis for the Content, Search, FAIR-o-meter, and Workflow pages that constitute the MIDAS Digital Commons. Results: Interoperability was limited by lack of standardization of input and output formats of software. When formats existed, they were human-readable specifications (22/24; 92%); only 3 formats (13%) had machine-readable specifications. Nevertheless, logical search of a triple store based on named data formats was able to identify scores of potentially interoperable combinations of software and datasets. Discussion: We improved the findability and availability of a sample of software and datasets and developed metrics for assessing interoperability. The barriers to interoperability included poor documentation of software input/output formats and little attention to standardization of most types of data in this field. Conclusion: Centralizing and formalizing the representation of digital objects within a commons promotes FAIRness, enables its measurement over time and the identification of potentially interoperable combinations of data and software.


BAND: Biomedical Alert News Dataset

Fu, Zihao, Zhang, Meiru, Meng, Zaiqiao, Shen, Yannan, Buckeridge, David, Collier, Nigel

arXiv.org Artificial Intelligence

Infectious disease outbreaks continue to pose a significant threat to human health and well-being. To improve disease surveillance and understanding of disease spread, several surveillance systems have been developed to monitor daily news alerts and social media. However, existing systems lack thorough epidemiological analysis in relation to corresponding alerts or news, largely due to the scarcity of well-annotated reports data. To address this gap, we introduce the Biomedical Alert News Dataset (BAND), which includes 1,508 samples from existing reported news articles, open emails, and alerts, as well as 30 epidemiology-related questions. These questions necessitate the model's expert reasoning abilities, thereby offering valuable insights into the outbreak of the disease. The BAND dataset brings new challenges to the NLP world, requiring better disguise capability of the content and the ability to infer important information. We provide several benchmark tasks, including Named Entity Recognition (NER), Question Answering (QA), and Event Extraction (EE), to show how existing models are capable of handling these tasks in the epidemiology domain. To the best of our knowledge, the BAND corpus is the largest corpus of well-annotated biomedical outbreak alert news with elaborately designed questions, making it a valuable resource for epidemiologists and NLP researchers alike.


Personalised dynamic super learning: an application in predicting hemodiafiltration's convection volumes

Chatton, Arthur, Bally, Michèle, Lévesque, Renée, Malenica, Ivana, Platt, Robert W., Schnitzer, Mireille E.

arXiv.org Machine Learning

Obtaining continuously updated predictions is a major challenge for personalised medicine. Leveraging combinations of parametric regressions and machine learning approaches, the personalised online super learner (POSL) can achieve such dynamic and personalised predictions. We adapt POSL to predict a repeated continuous outcome dynamically and propose a new way to validate such personalised or dynamic prediction models. We illustrate its performance by predicting the convection volume of patients undergoing hemodiafiltration. POSL outperformed its candidate learners with respect to median absolute error, calibration-in-the-large, discrimination, and net benefit. We finally discuss the choices and challenges underlying the use of POSL.


Supervised Machine Learning for Breast Cancer Risk Factors Analysis and Survival Prediction

Chtouki, Khaoula, Rhanoui, Maryem, Mikram, Mounia, Amazian, Kamelia, Yousfi, Siham

arXiv.org Artificial Intelligence

The choice of the most effective treatment may eventually be influenced by breast cancer survival prediction. To predict the chances of a patient surviving, a variety of techniques were employed, such as statistical, machine learning, and deep learning models. In the current study, 1904 patient records from the METABRIC dataset were utilized to predict a 5-year breast cancer survival using a machine learning approach. In this study, we compare the outcomes of seven classification models to evaluate how well they perform using the following metrics: recall, AUC, confusion matrix, accuracy, precision, false positive rate, and true positive rate. The findings demonstrate that the classifiers for Logistic Regression (LR), Support Vector Machines (SVM), Decision Tree (DT), Random Forest (RD), Extremely Randomized Trees (ET), K-Nearest Neighbor (KNN), and Adaptive Boosting (AdaBoost) can accurately predict the survival rate of the tested samples, which is 75,4\%, 74,7\%, 71,5\%, 75,5\%, 70,3\%, and 78 percent.


Application of targeted maximum likelihood estimation in public health and epidemiological studies: a systematic review

Smith, Matthew J., Phillips, Rachael V., Luque-Fernandez, Miguel Angel, Maringe, Camille

arXiv.org Machine Learning

The Targeted Maximum Likelihood Estimation (TMLE) statistical data analysis framework integrates machine learning, statistical theory, and statistical inference to provide a least biased, efficient and robust strategy for estimation and inference of a variety of statistical and causal parameters. We describe and evaluate the epidemiological applications that have benefited from recent methodological developments. We conducted a systematic literature review in PubMed for articles that applied any form of TMLE in observational studies. We summarised the epidemiological discipline, geographical location, expertise of the authors, and TMLE methods over time. We used the Roadmap of Targeted Learning and Causal Inference to extract key methodological aspects of the publications. We showcase the contributions to the literature of these TMLE results. Of the 81 publications included, 25% originated from the University of California at Berkeley, where the framework was first developed by Professor Mark van der Laan. By the first half of 2022, 70% of the publications originated from outside the United States and explored up to 7 different epidemiological disciplines in 2021-22. Double-robustness, bias reduction and model misspecification were the main motivations that drew researchers towards the TMLE framework. Through time, a wide variety of methodological, tutorial and software-specific articles were cited, owing to the constant growth of methodological developments around TMLE. There is a clear dissemination trend of the TMLE framework to various epidemiological disciplines and to increasing numbers of geographical areas. The availability of R packages, publication of tutorial papers, and involvement of methodological experts in applied publications have contributed to an exponential increase in the number of studies that understood the benefits, and adoption, of TMLE.