Identifying subgroups of patients who benefit from a treatment is a key aspect of personalized medicine, these subgroups can be used to develop individualized treatment rules (ITRs). Many machine learning methods have been proposed to create such rules. However, to what extent methods lead to the same ITRs, i.e., recommending the same treatment for the same individuals is unclear. To see if methods lead to similar ITRs, we compared the most common approaches in two randomized control trials. Two classes of methods can be distinguished to develop an ITR. The first class of methods relies on predicting individualized treatment effects from which an ITR is derived by recommending the evaluated treatment to the individuals with a predicted benefit. In the second class, methods directly estimate the ITR without estimating individualized treatment effects. For each trial, the performance of ITRs was assessed with various metrics, and the pairwise agreement between ITRs was also calculated. Results showed that the ITRs obtained by the different methods generally had considerable disagreements regarding the individuals to be treated. A better concordance was found among akin methods. Overall, when evaluating the performance of ITRs in a validation sample, all methods produced ITRs with limited performance, suggesting a high potential for overfitting. The different methods do not lead to similar ITRs and are therefore not interchangeable. The choice of the method has a lot of influence on which patients end up being given a certain treatment which draws some concerns about the practical use of the methods.
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Citation metrics are the best tools for research assessments. However, current metrics may be misleading in research systems that pursue simultaneously different goals, such as the advance of science and incremental innovations, because their publications have different citation distributions. We estimate the contribution to the progress of knowledge by studying only a limited number of the most cited papers, which are dominated by publications pursuing this progress. To field-normalize the metrics, we substitute the number of citations by the rank position of papers from one country in the global list of papers. Using synthetic series of lognormally distributed numbers, we developed the Rk-index, which is calculated from the global ranks of the 10 highest numbers in each series, and demonstrate its equivalence to the number of papers in top percentiles, P_top0.1% and P_top0.01% . In real cases, the Rk-index is simple and easy to calculate, and evaluates the contribution to the progress of knowledge better than less stringent metrics. Although further research is needed, rank analysis of the most cited papers is a promising approach for research evaluation. It is also demonstrated that, for this purpose, domestic and collaborative papers should be studied independently.
In causal inference studies, interest often lies in understanding the mechanisms through which a treatment affects an outcome. One approach is principal stratification (PS), which introduces well-defined causal effects in the presence of confounded post-treatment variables, or mediators, and clearly defines the assumptions for identification and estimation of those effects. The goal of this paper is to extend the PS framework to studies with continuous treatments and continuous post-treatment variables, which introduces a number of unique challenges both in terms of defining causal effects and performing inference. This manuscript provides three key methodological contributions: 1) we introduce novel principal estimands for continuous treatments that provide valuable insights into different causal mechanisms, 2) we utilize Bayesian nonparametric approaches to model the joint distribution of the potential mediating variables based on both Gaussian processes and Dirichlet process mixtures to ensure our approach is robust to model misspecification, and 3) we provide theoretical and numerical justification for utilizing a model for the potential outcomes to identify the joint distribution of the potential mediating variables. Lastly, we apply our methodology to a novel study of the relationship between the economy and arrest rates, and how this is potentially mediated by police capacity.
Reinforcement learning (RL) algorithms face the challenge of limited data efficiency, particularly when dealing with high-dimensional state spaces and large-scale problems. Most RL methods often rely solely on state transition information within the same episode when updating the agent's Critic, which can lead to low data efficiency and sub-optimal training time consumption. Inspired by human-like analogical reasoning abilities, we introduce a novel mesh information propagation mechanism, termed the 'Imagination Mechanism (IM)', designed to significantly enhance the data efficiency of RL algorithms. Specifically, IM enables information generated by a single sample to be effectively broadcasted to different states, instead of simply transmitting in the same episode and it allows the model to better understand the interdependencies between states and learn scarce sample information more efficiently. To promote versatility, we extend the imagination mechanism to function as a plug-and-play module that can be seamlessly and fluidly integrated into other widely adopted RL models. Our experiments demonstrate that Imagination mechanism consistently boosts four mainstream SOTA RL-algorithms, such as SAC, PPO, DDPG, and DQN, by a considerable margin, ultimately leading to superior performance than before across various tasks. For access to our code and data, please visit //github.com/Zero-coder/FECAM.
Personalized adaptive interventions offer the opportunity to increase patient benefits, however, there are challenges in their planning and implementation. Once implemented, it is an important question whether personalized adaptive interventions are indeed clinically more effective compared to a fixed gold standard intervention. In this paper, we present an innovative N-of-1 trial study design testing whether implementing a personalized intervention by an online reinforcement learning agent is feasible and effective. Throughout, we use a new study on physical exercise recommendations to reduce pain in endometriosis for illustration. We describe the design of a contextual bandit recommendation agent and evaluate the agent in simulation studies. The results show that adaptive interventions add complexity to the design and implementation process, but have the potential to improve patients' benefits even if only few observations are available. In order to quantify the expected benefit, data from previous interventional studies is required. We expect our approach to be transferable to other interventions and clinical interventions.
A problem related to the development of algorithms designed to find the structure of artificial neural network used for behavioural (black-box) modelling of selected dynamic processes has been addressed in this paper. The research has included four original proposals of algorithms dedicated to neural network architecture search. Algorithms have been based on well-known optimisation techniques such as evolutionary algorithms and gradient descent methods. In the presented research an artificial neural network of recurrent type has been used, whose architecture has been selected in an optimised way based on the above-mentioned algorithms. The optimality has been understood as achieving a trade-off between the size of the neural network and its accuracy in capturing the response of the mathematical model under which it has been learnt. During the optimisation, original specialised evolutionary operators have been proposed. The research involved an extended validation study based on data generated from a mathematical model of the fast processes occurring in a pressurised water nuclear reactor.
Out of the participants in a randomized experiment with anticipated heterogeneous treatment effects, is it possible to identify which subjects have a positive treatment effect? While subgroup analysis has received attention, claims about individual participants are much more challenging. We frame the problem in terms of multiple hypothesis testing: each individual has a null hypothesis (stating that the potential outcomes are equal, for example) and we aim to identify those for whom the null is false (the treatment potential outcome stochastically dominates the control one, for example). We develop a novel algorithm that identifies such a subset, with nonasymptotic control of the false discovery rate (FDR). Our algorithm allows for interaction -- a human data scientist (or a computer program) may adaptively guide the algorithm in a data-dependent manner to gain power. We show how to extend the methods to observational settings and achieve a type of doubly-robust FDR control. We also propose several extensions: (a) relaxing the null to nonpositive effects, (b) moving from unpaired to paired samples, and (c) subgroup identification. We demonstrate via numerical experiments and theoretical analysis that the proposed method has valid FDR control in finite samples and reasonably high identification power.
Epidemiologic and genetic studies in chronic obstructive pulmonary disease (COPD) and many complex diseases suggest subgroup disparities (e.g., by sex). We consider this problem from the standpoint of integrative analysis where we combine information from different views (e.g., genomics, proteomics, clinical data). Existing integrative analysis methods ignore the heterogeneity in subgroups, and stacking the views and accounting for subgroup heterogeneity does not model the association among the views. To address analytical challenges in the problem of our interest, we propose a statistical approach for joint association and prediction that leverages the strengths in each view to identify molecular signatures that are shared by and specific to males and females and that contribute to the variation in COPD, measured by airway wall thickness. HIP (Heterogeneity in Integration and Prediction) accounts for subgroup heterogeneity, allows for sparsity in variable selection, is applicable to multi-class and to univariate or multivariate continuous outcomes, and incorporates covariate adjustment. We develop efficient algorithms in PyTorch. Our COPD findings have identified several proteins, genes, and pathways that are common and specific to males and females, some of which have been implicated in COPD, while others could lead to new insights into sex differences in COPD mechanisms.
For randomized trials that use text as an outcome, traditional approaches for assessing treatment impact require that each document first be manually coded for constructs of interest by trained human raters. This process, the current standard, is both time-consuming and limiting: even the largest human coding efforts are typically constrained to measure only a small set of dimensions across a subsample of available texts. In this work, we present an inferential framework that can be used to increase the power of an impact assessment, given a fixed human-coding budget, by taking advantage of any ``untapped" observations -- those documents not manually scored due to time or resource constraints -- as a supplementary resource. Our approach, a methodological combination of causal inference, survey sampling methods, and machine learning, has four steps: (1) select and code a sample of documents; (2) build a machine learning model to predict the human-coded outcomes from a set of automatically extracted text features; (3) generate machine-predicted scores for all documents and use these scores to estimate treatment impacts; and (4) adjust the final impact estimates using the residual differences between human-coded and machine-predicted outcomes. As an extension to this approach, we also develop a strategy for identifying an optimal subset of documents to code in Step 1 in order to further enhance precision. Through an extensive simulation study based on data from a recent field trial in education, we show that our proposed approach can be used to reduce the scope of a human-coding effort while maintaining nominal power to detect a significant treatment impact.
Artificial neural networks thrive in solving the classification problem for a particular rigid task, acquiring knowledge through generalized learning behaviour from a distinct training phase. The resulting network resembles a static entity of knowledge, with endeavours to extend this knowledge without targeting the original task resulting in a catastrophic forgetting. Continual learning shifts this paradigm towards networks that can continually accumulate knowledge over different tasks without the need to retrain from scratch. We focus on task incremental classification, where tasks arrive sequentially and are delineated by clear boundaries. Our main contributions concern 1) a taxonomy and extensive overview of the state-of-the-art, 2) a novel framework to continually determine the stability-plasticity trade-off of the continual learner, 3) a comprehensive experimental comparison of 11 state-of-the-art continual learning methods and 4 baselines. We empirically scrutinize method strengths and weaknesses on three benchmarks, considering Tiny Imagenet and large-scale unbalanced iNaturalist and a sequence of recognition datasets. We study the influence of model capacity, weight decay and dropout regularization, and the order in which the tasks are presented, and qualitatively compare methods in terms of required memory, computation time, and storage.
Machine-learning models have demonstrated great success in learning complex patterns that enable them to make predictions about unobserved data. In addition to using models for prediction, the ability to interpret what a model has learned is receiving an increasing amount of attention. However, this increased focus has led to considerable confusion about the notion of interpretability. In particular, it is unclear how the wide array of proposed interpretation methods are related, and what common concepts can be used to evaluate them. We aim to address these concerns by defining interpretability in the context of machine learning and introducing the Predictive, Descriptive, Relevant (PDR) framework for discussing interpretations. The PDR framework provides three overarching desiderata for evaluation: predictive accuracy, descriptive accuracy and relevancy, with relevancy judged relative to a human audience. Moreover, to help manage the deluge of interpretation methods, we introduce a categorization of existing techniques into model-based and post-hoc categories, with sub-groups including sparsity, modularity and simulatability. To demonstrate how practitioners can use the PDR framework to evaluate and understand interpretations, we provide numerous real-world examples. These examples highlight the often under-appreciated role played by human audiences in discussions of interpretability. Finally, based on our framework, we discuss limitations of existing methods and directions for future work. We hope that this work will provide a common vocabulary that will make it easier for both practitioners and researchers to discuss and choose from the full range of interpretation methods.
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