Data Mining Techniques in Pharmacovigilance: Analysis of the Publicly Accessible FDA Adverse Event Reporting System (AERS)

Pharmacovigilance is a clinically oriented discipline, which may guide appropriate drug use through a balanced assessment of drug safety. Although much has been done in recent years, efforts are needed to expand the border of pharmacovigilance. We have provided insight into the FDA_Adverse Events Reporting Systems (FDA_AERS), a worldwide publicly available pharmacovigilance archive, to exemplify how to address major methodological issues. We believe that fostering discussion among researchers will increase transparency and facilitate definition of the most reliable approaches. By virtue of its large population coverage and free availability, the FDA_AERS has the potential to pave the way to a new way of looking to signal detection in PhV. Our key messages are: (1) before applying statistical tools (i.e., Data Mining Approaches - DMAs) to pharmacovigilance database for signal detection, all aspects related to data quality should be considered (e.g., drug mapping, missing data and duplicates); (2) at present, the choice of a given DMA mostly relies on local habits, expertise and attitude and there is room for improvement in this area; (3) DMA performance may be highly situation dependent; (4) over-reliance on these methods may have deleterious consequences, especially with the so-called "designated medical events", for which a case-by-case analysis is mandatory and complements disproportionality; and (5) the most appropriate selection of pharmacovigilance tools needs to be tailored to each situation, being mindful of the numerous biases and confounders that may influence performance and incremental utility of DMAs

Adverse Drug Reaction Mining in Pharmacovigilance data using Formal Concept Analysis

International audienceIn this paper we discuss the problem of extracting and evaluating associations between drugs and adverse effects in pharmacovigilance data. Approaches proposed by the medical informatics community for mining one drug - one effect pairs perform an exhaustive search strategy that precludes from mining high-order associations. Some specificities of pharmacovigilance data prevent from applying pattern mining approaches proposed by the data mining community for similar problems dealing with epidemiological studies. We argue that Formal Concept Analysis (FCA) and concept lattices constitute a suitable framework for both identifying relevant associations, and assisting experts in their evaluation task. Demographic attributes are handled so that the disproportionality of an association is computed w.r.t. the relevant population stratum to prevent confounding. We put the focus on the understandability of the results and provide evaluation facilities for experts. A real case study on a subset of the French spontaneous reporting system shows that the method identifies known adverse drug reactions and some unknown associations that has to be further investigated

Determining correspondences between high-frequency MedDRA concepts and SNOMED: a case study

<p>Abstract</p> <p>Background</p> <p>The Systematic Nomenclature of Medicine Clinical Terms (SNOMED CT) is being advocated as the foundation for encoding clinical documentation. While the electronic medical record is likely to play a critical role in pharmacovigilance - the detection of adverse events due to medications - classification and reporting of Adverse Events is currently based on the Medical Dictionary of Regulatory Activities (MedDRA). Complete and high-quality MedDRA-to-SNOMED CT mappings can therefore facilitate pharmacovigilance.</p> <p>The existing mappings, as determined through the Unified Medical Language System (UMLS), are partial, and record only one-to-one correspondences even though SNOMED CT can be used compositionally. Efforts to map previously unmapped MedDRA concepts would be most productive if focused on concepts that occur frequently in actual adverse event data.</p> <p>We aimed to identify aspects of MedDRA that complicate mapping to SNOMED CT, determine pattern in unmapped high-frequency MedDRA concepts, and to identify types of integration errors in the mapping of MedDRA to UMLS.</p> <p>Methods</p> <p>Using one years' data from the US Federal Drug Administrations Adverse Event Reporting System, we identified MedDRA preferred terms that collectively accounted for 95% of both Adverse Events and Therapeutic Indications records. After eliminating those already mapping to SNOMED CT, we attempted to map the remaining 645 Adverse-Event and 141 Therapeutic-Indications preferred terms with software assistance.</p> <p>Results</p> <p>All but 46 Adverse-Event and 7 Therapeutic-Indications preferred terms could be composed using SNOMED CT concepts: none of these required more than 3 SNOMED CT concepts to compose. We describe the common composition patterns in the paper. About 30% of both Adverse-Event and Therapeutic-Indications Preferred Terms corresponded to single SNOMED CT concepts: the correspondence was detectable by human inspection but had been missed during the integration process, which had created duplicated concepts in UMLS.</p> <p>Conclusions</p> <p>Identification of composite mapping patterns, and the types of errors that occur in the MedDRA content within UMLS, can focus larger-scale efforts on improving the quality of such mappings, which may assist in the creation of an adverse-events ontology.</p

Knowledge-based Biomedical Data Science 2019

Knowledge-based biomedical data science (KBDS) involves the design and implementation of computer systems that act as if they knew about biomedicine. Such systems depend on formally represented knowledge in computer systems, often in the form of knowledge graphs. Here we survey the progress in the last year in systems that use formally represented knowledge to address data science problems in both clinical and biological domains, as well as on approaches for creating knowledge graphs. Major themes include the relationships between knowledge graphs and machine learning, the use of natural language processing, and the expansion of knowledge-based approaches to novel domains, such as Chinese Traditional Medicine and biodiversity.Comment: Manuscript 43 pages with 3 tables; Supplemental material 43 pages with 3 table

Approximate Data Mining Techniques on Clinical Data

The past two decades have witnessed an explosion in the number of medical and healthcare datasets available to researchers and healthcare professionals. Data collection efforts are highly required, and this prompts the development of appropriate data mining techniques and tools that can automatically extract relevant information from data. Consequently, they provide insights into various clinical behaviors or processes captured by the data. Since these tools should support decision-making activities of medical experts, all the extracted information must be represented in a human-friendly way, that is, in a concise and easy-to-understand form. To this purpose, here we propose a new framework that collects different new mining techniques and tools proposed. These techniques mainly focus on two aspects: the temporal one and the predictive one. All of these techniques were then applied to clinical data and, in particular, ICU data from MIMIC III database. It showed the flexibility of the framework, which is able to retrieve different outcomes from the overall dataset. The first two techniques rely on the concept of Approximate Temporal Functional Dependencies (ATFDs). ATFDs have been proposed, with their suitable treatment of temporal information, as a methodological tool for mining clinical data. An example of the knowledge derivable through dependencies may be "within 15 days, patients with the same diagnosis and the same therapy usually receive the same daily amount of drug". However, current ATFD models are not analyzing the temporal evolution of the data, such as "For most patients with the same diagnosis, the same drug is prescribed after the same symptom". To this extent, we propose a new kind of ATFD called Approximate Pure Temporally Evolving Functional Dependencies (APEFDs). Another limitation of such kind of dependencies is that they cannot deal with quantitative data when some tolerance can be allowed for numerical values. In particular, this limitation arises in clinical data warehouses, where analysis and mining have to consider one or more measures related to quantitative data (such as lab test results and vital signs), concerning multiple dimensional (alphanumeric) attributes (such as patient, hospital, physician, diagnosis) and some time dimensions (such as the day since hospitalization and the calendar date). According to this scenario, we introduce a new kind of ATFD, named Multi-Approximate Temporal Functional Dependency (MATFD), which considers dependencies between dimensions and quantitative measures from temporal clinical data. These new dependencies may provide new knowledge as "within 15 days, patients with the same diagnosis and the same therapy receive a daily amount of drug within a fixed range". The other techniques are based on pattern mining, which has also been proposed as a methodological tool for mining clinical data. However, many methods proposed so far focus on mining of temporal rules which describe relationships between data sequences or instantaneous events, without considering the presence of more complex temporal patterns into the dataset. These patterns, such as trends of a particular vital sign, are often very relevant for clinicians. Moreover, it is really interesting to discover if some sort of event, such as a drug administration, is capable of changing these trends and how. To this extent, we propose a new kind of temporal patterns, called Trend-Event Patterns (TEPs), that focuses on events and their influence on trends that can be retrieved from some measures, such as vital signs. With TEPs we can express concepts such as "The administration of paracetamol on a patient with an increasing temperature leads to a decreasing trend in temperature after such administration occurs". We also decided to analyze another interesting pattern mining technique that includes prediction. This technique discovers a compact set of patterns that aim to describe the condition (or class) of interest. Our framework relies on a classification model that considers and combines various predictive pattern candidates and selects only those that are important to improve the overall class prediction performance. We show that our classification approach achieves a significant reduction in the number of extracted patterns, compared to the state-of-the-art methods based on minimum predictive pattern mining approach, while preserving the overall classification accuracy of the model. For each technique described above, we developed a tool to retrieve its kind of rule. All the results are obtained by pre-processing and mining clinical data and, as mentioned before, in particular ICU data from MIMIC III database