Yanqing Ji

A Potential Causal Association Mining Algorithm for Screening Adverse Drug Reactions in Postmarketing Surveillance

Early detection of unknown adverse drug reactions (ADRs) in postmarketing surveillance saves lives and prevents harmful consequences. We propose a novel data mining approach to signaling potential ADRs from electronic health databases. More specifically, we introduce potential causal association rules (PCARs) to represent the potential causal relationship between a drug and ICD-9 (CDC. (2010). International Classification of Diseases, Ninth Revision (ICD-9). [Online]. Available: http://www.cdc.gov/nchs/icd/icd9.html) coded signs or symptoms representing potential ADRs. Due to the infrequent nature of ADRs, the existing frequency-based data mining methods cannot effectively discover PCARs. We introduce a new interestingness measure, potential causal leverage, to quantify the degree of association of a PCAR. This measure is based on the computational, experience-based fuzzy recognition-primed decision (RPD) model that we developed previously (Y. Ji, R. M. Massanari, J. Ager, J. Yen, R. E. Miller, and H. Ying, “A fuzzy logic-based computational recognition-primed decision model,” Inf. Sci., vol. 177, pp. 4338-4353, 2007) on the basis of the well-known, psychology-originated qualitative RPD model (G. A. Klein, “A recognition-primed decision making model of rapid decision making,” in Decision Making in Action: Models and Methods, 1993, pp. 138-147). The potential causal leverage assesses the strength of the association of a drug-symptom pair given a collection of patient cases. To test our data mining approach, we retrieved electronic medical data for 16 206 patients treated by one or more than eight drugs of our interest at the Veterans Affairs Medical Center in Detroit between 2007 and 2009. We selected enalapril as the target drug for this ADR signal generation study. We used our algorithm to preliminarily evaluate the associations between enalapril and all the ICD-9 codes associated with it. The experimental results indicate that our approach has a potential to better signal potential ADRs than risk ratio and leverage, two traditional frequency-based measures. Among the top 50 signal pairs (i.e., enalapril versus symptoms) ranked by the potential causal-leverage measure, the physicians on the project determined that eight of them probably represent true causal associations.

A fuzzy logic-based computational recognition-primed decision model

The recognition-primed decision (RPD) model is a primary naturalistic decision-making approach which seeks to explicitly recognize how human decision makers handle complex tasks and environment based on their experience. Motivated by the need for quantitative computer modeling and simulation of human decision processes in various application domains, including medicine, we have developed a general-purpose computational fuzzy RPD model that utilizes fuzzy sets, fuzzy rules, and fuzzy reasoning to represent, interpret, and compute imprecise and subjective information in every aspect of the model. Experiences acquired by solicitation with experts are stored in experience knowledge bases. New local and global similarity measures have been developed to identify the experience that is most applicable to the current situation in a specific decision-making context. Furthermore, an action evaluation strategy has been developed to select the workable course of action. The proposed fuzzy RPD model has been preliminarily validated by using it to calculate the extent of causality between a drug (Cisapride, withdrawn by the FDA from the market in 2000) and some of its adverse effects for 100 hypothetical patients. The simulated patients were created based on the profiles of over 1000 actual patients treated with the drug at our medical center before its withdrawal. The model validity was demonstrated by comparing the decisions made by the proposed model and those by two independent internists. The levels of agreement were established by the weighted Kappa statistic and the results suggested good to excellent agreement.

A Method for Mining Infrequent Causal Associations and Its Application in Finding Adverse Drug Reaction Signal Pairs

In many real-world applications, it is important to mine causal relationships where an event or event pattern causes certain outcomes with low probability. Discovering this kind of causal relationships can help us prevent or correct negative outcomes caused by their antecedents. In this paper, we propose an innovative data mining framework and apply it to mine potential causal associations in electronic patient data sets where the drug-related events of interest occur infrequently. Specifically, we created a novel interestingness measure, exclusive causal-leverage, based on a computational, fuzzy recognition-primed decision (RPD) model that we previously developed. On the basis of this new measure, a data mining algorithm was developed to mine the causal relationship between drugs and their associated adverse drug reactions (ADRs). The algorithm was tested on real patient data retrieved from the Veterans Affairs Medical Center in Detroit, Michigan. The retrieved data included 16,206 patients (15,605 male, 601 female). The exclusive causal-leverage was employed to rank the potential causal associations between each of the three selected drugs (i.e., enalapril, pravastatin, and rosuvastatin) and 3,954 recorded symptoms, each of which corresponded to a potential ADR. The top 10 drug-symptom pairs for each drug were evaluated by the physicians on our project team. The numbers of symptoms considered as likely real ADRs for enalapril, pravastatin, and rosuvastatin were 8, 7, and 6, respectively. These preliminary results indicate the usefulness of our method in finding potential ADR signal pairs for further analysis (e.g., epidemiology study) and investigation (e.g., case review) by drug safety professionals.

A Distributed, Collaborative Intelligent Agent System Approach for Proactive Postmarketing Drug Safety Surveillance

Discovering unknown adverse drug reactions (ADRs) in postmarketing surveillance as early as possible is of great importance. The current approach to postmarketing surveillance primarily relies on spontaneous reporting. It is a passive surveillance system and limited by gross underreporting (<10% reporting rate), latency, and inconsistent reporting. We propose a novel team-based intelligent agent software system approach for proactively monitoring and detecting potential ADRs of interest using electronic patient records. We designed such a system and named it ADRMonitor. The intelligent agents, operating on computers located in different places, are capable of continuously and autonomously collaborating with each other and assisting the human users (e.g., the food and drug administration (FDA), drug safety professionals, and physicians). The agents should enhance current systems and accelerate early ADR identification. To evaluate the performance of the ADRMonitor with respect to the current spontaneous reporting approach, we conducted simulation experiments on identification of ADR signal pairs (i.e., potential links between drugs and apparent adverse reactions) under various conditions. The experiments involved over 275 000 simulated patients created on the basis of more than 1000 real patients treated by the drug cisapride that was on the market for seven years until its withdrawal by the FDA in 2000 due to serious ADRs. Healthcare professionals utilizing the spontaneous reporting approach and the ADRMonitor were separately simulated by decision-making models derived from a general cognitive decision model called fuzzy recognition-primed decision (RPD) model that we recently developed. The quantitative simulation results show that 1) the number of true ADR signal pairs detected by the ADRMonitor is 6.6 times higher than that by the spontaneous reporting strategy; 2) the ADR detection rate of the ADRMonitor agents with even moderate decision-making skills is five times higher than that of spontaneous reporting; and 3) as the number of patient cases increases, ADRs could be detected significantly earlier by the ADRMonitor.

A distributed adverse drug reaction detection system using intelligent agents with a fuzzy recognition-primed decision model

Discovering unknown adverse drug reactions (ADRs) in postmarketing surveillance as early as possible is highly desirable. Nevertheless, current postmarketing surveillance methods largely rely on spontaneous reports that suffer from serious underreporting, latency, and inconsistent reporting. Thus these methods are not ideal for rapidly identifying rare ADRs. The multiagent systems paradigm is an emerging and effective approach to tackling distributed problems, especially when data sources and knowledge are geographically located in different places and coordination and collaboration are necessary for decision making. In this article, we propose an active, multiagent framework for early detection of ADRs by utilizing electronic patient data distributed across many different sources and locations. In this framework, intelligent agents assist a team of experts based on the well‐known human decision‐making model called Recognition‐Primed Decision (RPD). We generalize the RPD model to a fuzzy RPD model and utilize fuzzy logic technology to not only represent, interpret, and compute imprecise and subjective cues that are commonly encountered in the ADR problem but also to retrieve prior experiences by evaluating the extent of matching between the current situation and a past experience. We describe our preliminary multiagent system design and illustrate its potential benefits for assisting expert teams in early detection of previously unknown ADRs.

A fuzzy recognition-primed decision model-based causal association mining algorithm for detecting adverse drug reactions in postmarketing surveillance

The current approach to postmarketing surveillance primarily relies on spontaneous reporting. It is a passive surveillance system and limited by gross underreporting (<10% reporting rate), latency, and inconsistent reporting. We propose a new interestingness measure, causal-leverage, to signal potential adverse drug reactions (ADRs) from electronic health databases which are readily available in most modern hospitals. This measure is based on an experience-based fuzzy recognition-primed decision (RPD) model that we developed previously [1] which assesses the strength of association of a drug-ADR pair within each individual patient case. Using the causal-leverage measure, we develop a data mining algorithm to evaluate the associations between a given drug enalapril and all potential ADRs in a real-world electronic health database. The experimental results have shown that our approach can effectively shortlist some known ADRs. For example, the known ADR hyperkalemia caused by enalapril was ranked as top 1% among all the 3954 potential ADRs in our database.

Modern Computational Techniques for the HMMER Sequence Analysis

This paper focuses on the latest research and critical reviews on modern computing architectures, software and hardware accelerated algorithms for bioinformatics data analysis with an emphasis on one of the most important sequence analysis applications—hidden Markov models (HMM). We show the detailed performance comparison of sequence analysis tools on various computing platforms recently developed in the bioinformatics society. The characteristics of the sequence analysis, such as data and compute-intensive natures, make it very attractive to optimize and parallelize by using both traditional software approach and innovated hardware acceleration technologies.

Mining Infrequent Causal Associations in Electronic Health Databases

Discovering infrequent causal relationships can help us prevent or correct negative outcomes caused by their antecedents. In this paper, we propose an innovative data mining framework and apply it to mine potential causal associations in electronic patient datasets where the drug-related events of interest occur infrequently. Specifically, we created a novel interestingness measure, exclusive causal-leverage, based on a computational, fuzzy recognition-primed decision (RPD) model that we previously developed. On the basis of this new measure, a data mining algorithm was developed to mine the causal relationship between drugs and their associated adverse drug reactions (ADRs). The algorithm was tested on real patient data retrieved from the Veterans Affairs Medical Center in Detroit, Michigan. The exclusive causal-leverage was employed to rank the potential causal associations between each of the two selected drugs (i.e., enalapril and pravastatin) and 3,954 recorded symptoms, each of which corresponds to a potential ADR. The top 10 drug-symptom pairs for each drug were evaluated by our physicians on the project team. The results showed that the number of symptoms considered as real ADRs for enalapril and pravastatin was 8 and 7 out of 10, respectively.

Finding similar patients in a multi-agent environment

Finding similar patients is highly desirable in many clinical applications. In this paper, we address the issue of how to find similar patients in a multi-agent environment where software agents, located in different places, work collaboratively and proactively help one another to empower their human users to achieve a common healthcare goal. We show how the agents, equipped with fuzzy similarity rules developed by the physicians on the team, collaborate to find similar patients in each agents patient database. We describe the architecture, design and implementation of the system. Using the popular agent language JADE and clinical information on 1,000 patients treated at the Detroit Veterans Affairs Medical Center, we have implemented a five-agent system and generated some preliminary simulation results.

Leveraging MapReduce to efficiently extract associations between biomedical concepts from large text data

Large biomedical text data represents an important source of information that not only enables researchers to discover in-depth knowledge about biological systems, but also helps healthcare professionals do evidence-based medicine in clinical settings. However, investigating and analyzing these data is often both data-intensive and computation-intensive. In this paper, we investigate how to use MapReduce, a parallel and distributed programming paradigm, to efficiently mine the associations between biomedical concepts extracted from a large set of biomedical articles. First, biomedical concepts were obtained by matching text to Unified Medical Language System (UMLS) Metathesaurus, a biomedical vocabulary and standard database. Then we developed a MapReduce algorithm that could be used to calculate a category of interestingness measures defined on the basis of a 22 contingency table. This algorithm consists of two MapReduce jobs and takes a stripes approach to reduce the number of intermediate results. Experiments were conducted using Amazon Elastic MapReduce (EMR) with an input of 33,960 articles from TREC (Text REtrieval Conference) 2006 Genomics Track. Performance test indicated that our algorithm had approximately linear scalability and was more efficient than a pairs approach in the literature. The physician in our project team evaluated a subset of the association mining results related to drug-disease treatment and found that meaningful association rules ranked high.