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Register a new userSupervised Adverse Drug Reaction Signalling Framework Imitating Bradford Hills Causality Considerations
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Added by
Uwe Aickelin
Publication date
2016
fields
Informatics Engineering
and research's language is
English
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Big longitudinal observational medical data potentially hold a wealth of information and have been recognised as potential sources for gaining new drug safety knowledge. Unfortunately there are many complexities and underlying issues when analysing longitudinal observational data. Due to these complexities, existing methods for large-scale detection of negative side effects using observational data all tend to have issues distinguishing between association and causality. New methods that can better discriminate causal and non-causal relationships need to be developed to fully utilise the data. In this paper we propose using a set of causality considerations developed by the epidemiologist Bradford Hill as a basis for engineering features that enable the application of supervised learning for the problem of detecting negative side effects. The Bradford Hill considerations look at various perspectives of a drug and outcome relationship to determine whether it shows causal traits. We taught a classifier to find patterns within these perspectives and it learned to discriminate between association and causality. The novelty of this research is the combination of supervised learning and Bradford Hills causality considerations to automate the Bradford Hills causality assessment. We evaluated the framework on a drug safety gold standard know as the observational medical outcomes partnerships nonspecified association reference set. The methodology obtained excellent discriminate ability with area under the curves ranging between 0.792-0.940 (existing method optimal: 0.73) and a mean average precision of 0.640 (existing method optimal: 0.141). The proposed features can be calculated efficiently and be readily updated, making the framework suitable for big observational data.
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Purpose: To develop a framework for identifying and incorporating candidate confounding interaction terms into a regularised cox regression analysis to refine adverse drug reaction signals obtained via longitudinal observational data. Methods: We considered six drug families that are commonly associated with myocardial infarction in observational healthcare data, but where the causal relationship ground truth is known (adverse drug reaction or not). We applied emergent pattern mining to find itemsets of drugs and medical events that are associated with the development of myocardial infarction. These are the candidate confounding interaction terms. We then implemented a cohort study design using regularised cox regression that incorporated and accounted for the candidate confounding interaction terms. Results The methodology was able to account for signals generated due to confounding and a cox regression with elastic net regularisation correctly ranked the drug families known to be true adverse drug reactions above those.
Autonomous driving systems have a pipeline of perception, decision, planning, and control. The decision module processes information from the perception module and directs the execution of downstream planning and control modules. On the other hand, the recent success of deep learning suggests that this pipeline could be replaced by end-to-end neural control policies, however, safety cannot be well guaranteed for the data-driven neural networks. In this work, we propose a hybrid framework to learn neural decisions in the classical modular pipeline through end-to-end imitation learning. This hybrid framework can preserve the merits of the classical pipeline such as the strict enforcement of physical and logical constraints while learning complex driving decisions from data. To circumvent the ambiguous annotation of human driving decisions, our method learns high-level driving decisions by imitating low-level control behaviors. We show in the simulation experiments that our modular driving agent can generalize its driving decision and control to various complex scenarios where the rule-based programs fail. It can also generate smoother and safer driving trajectories than end-to-end neural policies.
Side effects of prescribed medications are a common occurrence. Electronic healthcare databases present the opportunity to identify new side effects efficiently but currently the methods are limited due to confounding (i.e. when an association between two variables is identified due to them both being associated to a third variable). In this paper we propose a proof of concept method that learns common associations and uses this knowledge to automatically refine side effect signals (i.e. exposure-outcome associations) by removing instances of the exposure-outcome associations that are caused by confounding. This leaves the signal instances that are most likely to correspond to true side effect occurrences. We then calculate a novel measure termed the confounding-adjusted risk value, a more accurate absolute risk value of a patient experiencing the outcome within 60 days of the exposure. Tentative results suggest that the method works. For the four signals (i.e. exposure-outcome associations) investigated we are able to correctly filter the majority of exposure-outcome instances that were unlikely to correspond to true side effects. The method is likely to improve when tuning the association rule mining parameters for specific health outcomes. This paper shows that it may be possible to filter signals at a patient level based on association rules learned from considering patients medical histories. However, additional work is required to develop a way to automate the tuning of the methods parameters.
Causality knowledge is crucial for many artificial intelligence systems. Conventional textual-based causality knowledge acquisition methods typically require laborious and expensive human annotations. As a result, their scale is often limited. Moreover, as no context is provided during the annotation, the resulting causality knowledge records (e.g., ConceptNet) typically do not take the context into consideration. To explore a more scalable way of acquiring causality knowledge, in this paper, we jump out of the textual domain and investigate the possibility of learning contextual causality from the visual signal. Compared with pure text-based approaches, learning causality from the visual signal has the following advantages: (1) Causality knowledge belongs to the commonsense knowledge, which is rarely expressed in the text but rich in videos; (2) Most events in the video are naturally time-ordered, which provides a rich resource for us to mine causality knowledge from; (3) All the objects in the video can be used as context to study the contextual property of causal relations. In detail, we first propose a high-quality dataset Vis-Causal and then conduct experiments to demonstrate that with good language and visual representation models as well as enough training signals, it is possible to automatically discover meaningful causal knowledge from the videos. Further analysis also shows that the contextual property of causal relations indeed exists, taking which into consideration might be crucial if we want to use the causality knowledge in real applications, and the visual signal could serve as a good resource for learning such contextual causality.
Causality is crucial to understanding the mechanisms behind complex systems and making decisions that lead to intended outcomes. Event sequence data is widely collected from many real-world processes, such as electronic health records, web clickstreams, and financial transactions, which transmit a great deal of information reflecting the causal relations among event types. Unfortunately, recovering causalities from observational event sequences is challenging, as the heterogeneous and high-dimensional event variables are often connected to rather complex underlying event excitation mechanisms that are hard to infer from limited observations. Many existing automated causal analysis techniques suffer from poor explainability and fail to include an adequate amount of human knowledge. In this paper, we introduce a visual analytics method for recovering causalities in event sequence data. We extend the Granger causality analysis algorithm on Hawkes processes to incorporate user feedback into causal model refinement. The visualization system includes an interactive causal analysis framework that supports bottom-up causal exploration, iterative causal verification and refinement, and causal comparison through a set of novel visualizations and interactions. We report two forms of evaluation: a quantitative evaluation of the model improvements resulting from the user-feedback mechanism, and a qualitative evaluation through case studies in different application domains to demonstrate the usefulness of the system.
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