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Towards Outcome-Driven Patient Subgroups: A Machine Learning Analysis Across Six Depression Treatment Studies
Mar 30, 2023
Major depressive disorder (MDD) is a heterogeneous condition; multiple underlying neurobiological substrates could be associated with treatment response variability. Understanding the sources of this variability and predicting outcomes has been elusive. Machine learning has shown promise in predicting treatment response in MDD, but one limitation has been the lack of clinical interpretability of machine learning models. We analyzed data from six clinical trials of pharmacological treatment for depression (total n = 5438) using the Differential Prototypes Neural Network (DPNN), a neural network model that derives patient prototypes which can be used to derive treatment-relevant patient clusters while learning to generate probabilities for differential treatment response. A model classifying remission and outputting individual remission probabilities for five first-line monotherapies and three combination treatments was trained using clinical and demographic data. Model validity and clinical utility were measured based on area under the curve (AUC) and expected improvement in sample remission rate with model-guided treatment, respectively. Post-hoc analyses yielded clusters (subgroups) based on patient prototypes learned during training. Prototypes were evaluated for interpretability by assessing differences in feature distributions and treatment-specific outcomes. A 3-prototype model achieved an AUC of 0.66 and an expected absolute improvement in population remission rate compared to the sample remission rate. We identified three treatment-relevant patient clusters which were clinically interpretable. It is possible to produce novel treatment-relevant patient profiles using machine learning models; doing so may improve precision medicine for depression. Note: This model is not currently the subject of any active clinical trials and is not intended for clinical use.
bartMachine: Machine Learning with Bayesian Additive Regression Trees
Nov 24, 2014
We present a new package in R implementing Bayesian additive regression trees (BART). The package introduces many new features for data analysis using BART such as variable selection, interaction detection, model diagnostic plots, incorporation of missing data and the ability to save trees for future prediction. It is significantly faster than the current R implementation, parallelized, and capable of handling both large sample sizes and high-dimensional data.
Prediction with Missing Data via Bayesian Additive Regression Trees
Feb 12, 2014
We present a method for incorporating missing data in non-parametric statistical learning without the need for imputation. We focus on a tree-based method, Bayesian Additive Regression Trees (BART), enhanced with "Missingness Incorporated in Attributes," an approach recently proposed incorporating missingness into decision trees (Twala, 2008). This procedure takes advantage of the partitioning mechanisms found in tree-based models. Simulations on generated models and real data indicate that our proposed method can forecast well on complicated missing-at-random and not-missing-at-random models as well as models where missingness itself influences the response. Our procedure has higher predictive performance and is more stable than competitors in many cases. We also illustrate BART's abilities to incorporate missingness into uncertainty intervals and to detect the influence of missingness on the model fit.