Using Big Data Analytics and Statistical Methods for Improving Drug Safety

This dissertation includes three studies, all focusing on utilizing Big Data and statistical methods for improving one of the most important aspects of health care, namely drug safety. In these studies we develop data analytics methodologies to inspect, clean, and model data with the aim of fulfilling the three main goals of drug safety; detection, understanding, and prediction of adverse drug effects.In the first study, we develop a methodology by combining both analytics and statistical methods with the aim of detecting associations between drugs and adverse events through historical patients' records. Particularly we show applicability of the developed methodology by focusing on investigating potential confounding role of common diabetes drugs on developing acute renal failure in diabetic patients. While traditional methods of signal detection mostly consider one drug and one adverse event at a time for investigation, our proposed methodology takes into account the effect of drug-drug interactions by identifying groups of drugs frequently prescribed together.In the second study, two independent methodologies are developed to investigate the role of prescription sequence factor on the likelihood of developing adverse events. In fact, this study focuses on using data analytics for understanding drug-event associations. Our analyses on the historical medication records of a group of diabetic patients using the proposed approaches revealed that the sequence in which the drugs are prescribed, and administered, significantly do matter in the development of adverse events associated with those drugs.The third study uses a chronological approach to develop a network of approved drugs and their known adverse events. It then utilizes a set of network metrics, both similarity- and centrality-based, to build and train machine learning predictive models and predict the likely adverse events for the newly discovered drugs before their approval and introduction to the market. For this purpose, data of known drug-event associations from a large biomedical publication database (i.e., PubMed) is employed to construct the network. The results indicate significant improvements in terms of accuracy of prediction of drug-evet associations compared with similar approaches

A conceptual framework on health professionals' engagement towards pharmacovigilance: a qualitative exploration

Background: With the growing reliance on drug therapy in the recent era, the safety of medications is one of the vital parameters for the success of any medicine. Considering this, pharmacovigilance (PV) was developed to provide adequate identification, reporting, evaluation, and understanding of adverse drug reactions (ADR). The objective of this study was to understand the opinion of health care providers on PV, the current reporting mechanisms, identifying the causes for underreporting, and the existing process in clinical practice.Methods: A qualitative study using pretested interview guide was conducted among 20 different cadres of healthcare personnel (doctors, pharmacists, and staff nurses) from various hospitals such as government, private, corporate, and medical college of Odisha state. The data were analysed using a thematic analysis. The meaning units have been identified from the transcript and coded with MAXQDA software (MAXQDA Analytics Pro 2020, VERBI GmbH Berlin).Results: Participants showed a lack of awareness regarding the concept of PV. A cluster of challenges such as lack of ADR monitoring, non-conducive work atmosphere and lack of cooperation between staff, lack of knowledge among the health professionals, and fear of legal liability as major pitfalls causing poor ADR reporting. To enhance the pharmacovigilance practice, participants suggested context-specific strategies such as IEC activities, innovative ideas to improve ADR monitoring, regular monitoring.Conclusions: Capacity building through training, regular monitoring and supervision to strengthen the pharmacovigilance practices is the current need in India

Analyzing adverse drug reaction using statistical and machine learning methods: A systematic review

Background: Adverse drug reactions (ADRs) are unintended negative drug-induced responses. Determining the association between drugs and ADRs is crucial, and several methods have been proposed to demonstrate this association. This systematic review aimed to examine the analytical tools by considering original articles that utilized statistical and machine learning methods for detecting ADRs. Methods: A systematic literature review was conducted based on articles published between 2015 and 2020. The keywords used were statistical, machine learning, and deep learning methods for detecting ADR signals. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. Results: We reviewed 72 articles, of which 51 and 21 addressed statistical and machine learning methods, respectively. Electronic medical record (EMR) data were exclusively analyzed using the regression method. For FDA Adverse Event Reporting System (FAERS) data, components of the disproportionality method were preferable. DrugBank was the most used database for machine learning. Other methods accounted for the highest and supervised methods accounted for the second highest. Conclusions: Using the 72 main articles, this review provides guidelines on which databases are frequently utilized and which analysis methods can be connected. For statistical analysis, >90% of the cases were analyzed by disproportionate or regression analysis with each spontaneous reporting system (SRS) data or electronic medical record (EMR) data; for machine learning research, however, there was a strong tendency to analyze various data combinations. Only half of the DrugBank database was occupied, and the k-nearest neighbor method accounted for the greatest proportion.ope

Machine learning in pharmaceutical services : an integrative review

A crescente digitalização e aplicação de inteligência artificial (IA) em problemas complexos do mundo real, tem potencial de melhorar os serviços de saúde, inclusive da atuação dos farmacêuticos no processo do cuidado. O objetivo deste estudo foi identificar na literatura científica, estudos que testam algoritmos de aprendizado de máquina (Machine Learning – ML) aplicados as atividades de farmacêuticos clínicos no cuidado ao paciente. Trata-se de uma revisão integrativa, realizada nas bases de dados, Pubmed, Portal BVS, Cochrane Library e Embase. Artigos originais, relacionados ao objetivo proposto, disponíveis e publicados antes de 31 de dezembro de 2021, foram incluídos, sem limitações de idioma. Foram encontrados 831 artigos, sendo 5 incluídos relacionados as atividades inseridas nos serviços de revisão da farmacoterapia (3) e monitorização terapêutica (2). Foram utilizadas técnicas supervisionadas (3) e não supervisionadas (2) de ML, com variedade de algoritmos testados, sendo todos os estudos publicados recentemente (2019-2021). Conclui-se que a aplicação da IA na farmácia clínica, ainda é discreta, sinalizando os desafios da era digital.The growing application of artificial intelligence (AI) in complex real-world problems has shown an enormous potential to improve health services, including the role of pharmacists in the care process. Thus, the objective of this study was to identify, in the scientific literature, studies that addressed the use of machine learning (ML) algorithms applied to the activities of clinical pharmacists in patient care. This is an integrative review, conducted in the databases Pubmed, VHL Regional Portal, Cochrane Library and Embase. Original articles, related to the proposed topic, which were available and published before December 31, 2021, were included, without language limitations. There were 831 articles retrieved 5 of which were related to activities included in the pharmacotherapy review services (3) and therapeutic monitoring (2). Supervised (3) and unsupervised (2) ML techniques were used, with a variety of algorithms tested, with all studies published recently (2019–2021). It is concluded that the application of AI in clinical pharmacy is still discreet, signaling the challenges of the digital age

Aprendizado de máquina nos serviços farmacêuticos: uma revisão integrativa

The growing application of artificial intelligence (AI) in complex real-world problems has shown an enormous potential to improve health services, including the role of pharmacists in the care process. Thus, the objective of this study was to identify, in the scientific literature, studies that addressed the use of machine learning (ML) algorithms applied to the activities of clinical pharmacists in patient care. This is an integrative review, conducted in the databases Pubmed, VHL Regional Portal, Cochrane Library and Embase. Original articles, related to the proposed topic, which were available and published before December 31, 2021, were included, without language limitations. There were 831 articles retrieved 5 of which were related to activities included in the pharmacotherapy review services (3) and therapeutic monitoring (2). Supervised (3) and unsupervised (2) ML techniques were used, with a variety of algorithms tested, with all studies published recently (2019 - 2021). It is concluded that the application of AI in clinical pharmacy is still discreet, signaling the challenges of the digital age.A crescente digitalização e aplicação de inteligência artificial (IA) em problemas complexos do mundo real, tem potencial de melhorar os serviços de saúde, inclusive da atuação dos farmacêuticos no processo do cuidado. O objetivo deste estudo foi identificar na literatura científica, estudos que testam algoritmos de aprendizado de máquina (Machine Learning - ML) aplicados as atividades de farmacêuticos clínicos no cuidado ao paciente. Trata-se de uma revisão integrativa, realizada nas bases de dados, Pubmed, Portal BVS, Cochrane Library e Embase. Artigos originais, relacionados ao objetivo proposto, disponíveis e publicados antes de 31 de dezembro de 2021, foram incluídos, sem limitações de idioma. Foram encontrados 831 artigos, sendo 5 incluídos relacionados as atividades inseridas nos serviços de revisão da farmacoterapia (3) e monitorização terapêutica (2). Foram utilizadas técnicas supervisionadas (3) e não supervisionadas (2) de ML, com variedade de algoritmos testados, sendo todos os estudos publicados recentemente (2019 - 2021). Conclui-se que a aplicação da IA na farmácia clínica, ainda é discreta, sinalizando os desafios da era digital.A crescente digitalização e aplicação de inteligência artificial (IA) em problemas complexos do mundo real, tem potencial de melhorar os serviços de saúde, inclusive da atuação dos farmacêuticos no processo do cuidado. O objetivo deste estudo foi identificar na literatura científica, estudos que testam algoritmos de aprendizado de máquina (Machine Learning - ML) aplicados as atividades de farmacêuticos clínicos no cuidado ao paciente. Trata-se de uma revisão integrativa, realizada nas bases de dados, Pubmed, Portal BVS, Cochrane Library e Embase. Artigos originais, relacionados ao objetivo proposto, disponíveis e publicados antes de 31 de dezembro de 2021, foram incluídos, sem limitações de idioma. Foram encontrados 831 artigos, sendo 5 incluídos relacionados as atividades inseridas nos serviços de revisão da farmacoterapia (3) e monitorização terapêutica (2). Foram utilizadas técnicas supervisionadas (3) e não supervisionadas (2) de ML, com variedade de algoritmos testados, sendo todos os estudos publicados recentemente (2019 - 2021). Conclui-se que a aplicação da IA na farmácia clínica, ainda é discreta, sinalizando os desafios da era digital

Digital Pharmacovigilance: the medwatcher system for monitoring adverse events through automated processing of internet social media and crowdsourcing

Thesis (Ph.D.)--Boston UniversityHalf of Americans take a prescription drug, medical devices are in broad use, and population coverage for many vaccines is over 90%. Nearly all medical products carry risk of adverse events (AEs), sometimes severe. However, pre- approval trials use small populations and exclude participants by specific criteria, making them insufficient to determine the risks of a product as used in the population. Existing post-marketing reporting systems are critical, but suffer from underreporting. Meanwhile, recent years have seen an explosion in adoption of Internet services and smartphones. MedWatcher is a new system that harnesses emerging technologies for pharmacovigilance in the general population. MedWatcher consists of two components, a text-processing module, MedWatcher Social, and a crowdsourcing module, MedWatcher Personal. With the natural language processing component, we acquire public data from the Internet, apply classification algorithms, and extract AE signals. With the crowdsourcing application, we provide software allowing consumers to submit AE reports directly. Our MedWatcher Social algorithm for identifying symptoms performs with 77% precision and 88% recall on a sample of Twitter posts. Our machine learning algorithm for identifying AE-related posts performs with 68% precision and 89% recall on a labeled Twitter corpus. For zolpidem tartrate, certolizumab pegol, and dimethyl fumarate, we compared AE profiles from Twitter with reports from the FDA spontaneous reporting system. We find some concordance (Spearman's rho= 0.85, 0.77, 0.82, respectively, for symptoms at MedDRA System Organ Class level). Where the sources differ, milder effects are overrepresented in Twitter. We also compared post-marketing profiles with trial results and found little concordance. MedWatcher Personal saw substantial user adoption, receiving 550 AE reports in a one-year period, including over 400 for one device, Essure. We categorized 400 Essure reports by symptom, compared them to 129 reports from the FDA spontaneous reporting system, and found high concordance (rho = 0.65) using MedDRA Preferred Term granularity. We also compared Essure Twitter posts with MedWatcher and FDA reports, and found rho= 0.25 and 0.31 respectively. MedWatcher represents a novel pharmacoepidemiology surveillance informatics system; our analysis is the first to compare AEs across social media, direct reporting, FDA spontaneous reports, and pre-approval trials

Prescribing Psychotropics: Misuse, Abuse, Dependence, Withdrawal and Addiction

© 2021 Papazisis, Spachos, Siafis, Pandria, Deligianni, Tsakiridis and Goulas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Recently, the growing use of prescription drugs for recreational purposes has been reported widely in the literature. However, the true extent and nature of such use is not completely understood. Some medications are already known to be misused. For instance, opioids, Central Nervous System (CNS) depressants (including tranquilizers, sedatives, and hypnotics) and stimulants (e.g. Attention-Deficit/Hyperactivity Disorder-medications). However, for a range of remaining molecules there have been anecdotal reports of misuse and diversion, but more needs to be understood. ‘Pharming’; ‘pharm-parties’; and ‘doctor-shopping’ attitudes, involving high-/ mega-dosage prescription drugs’ intake, are new trends which are increasingly being reported among young adult populations. Increasing levels of access to the web over the past 15 years or so may have boosted the current scenario of prescribed drugs’ misuse and abuse, with social networks playing a role in prescription drugs’ aggressive marketing/ distribution from rogue ‘pharmacy’ websites. Consistent with this, the current Research Topic will cover the assessment of the misuse, abuse, dependence, withdrawal, diversion and addiction potential of prescribing drugs. Most of these drugs are not scheduled, and there is little or no indication of these putative misusing issues in their accompanying medication package. Furthermore, some of these medications are made available over-the-counter in a range of countries. Prescribing drugs, which are the focus of this Research Topic, include but are definitely not limited to: gabapentinoids, antidepressants, antipsychotics, Z-drugs, beta-agonists, and over-the-counter medications (e.g., codeine phosphate; loperamide, dextromethorphan, promethazine, etc). The Research Topic would welcome empirical papers, systematic reviews, meta-analysis, reviews, and brief reports. Special consideration will be given to: • Pre-marketing considerations on how to identify the possible CNS drugs’ addictive liability levels • Post-marketing surveillance and pharmacovigilance strategies able to detect early signals of drug abuse (e.g., monitoring of drug utilization, anonymous tracking of users’ posts on social media, analysis of international Adverse Drug Reactions’ databases entries) • Clinical data • Methods for optimal reduction strategies to come off prescribing psychotropics, including antidepressants • Analysis of the current measures adopted to reduce drug diversio

Predicting Adverse Effects of Drugs

The number of drugs currently available at the commercial level is quite large. The therapeutic importance and the benefit of these are indisputable. However, unknown effects of individual drugs and/or the interaction of effects between drugs may have serious consequences for the health of the population.The use of some drugs may prove to be unsafe and risky, since the response and interaction of the population to their use differ substantially. It is known that in practice and despite all measures taken during the premarketing phase they may be insufficient, since factors such as the patients age, clinical history and interaction with other medicinal products may be at the apex of these undesirable effects.This report gives an overview of existing studies of detection and prevention of adverse drug effects and the possible contribution of informatics to the diagnosis of this problem. We go one step further and, propose to study and apply the use of Data Mining techniques to prevent the adverse effects of drugs

Knowledge Management approaches to model pathophysiological mechanisms and discover drug targets in Multiple Sclerosis

Multiple Sclerosis (MS) is one of the most prevalent neurodegenerative diseases for which a cure is not yet available. MS is a complex disease for numerous reasons; its etiology is unknown, the diagnosis is not exclusive, the disease course is unpredictable and therapeutic response varies from patient to patient. There are four established subtypes of MS, which are segregated based on different characteristics. Many environmental and genetic factors are considered to play a role in MS etiology, including viral infection, vitamin D deficiency, epigenetical changes and some genes. Despite the large body of diverse scientific knowledge, from laboratory findings to clinical trials, no integrated model which portrays the underlying mechanisms of the disease state of MS is available. Contemporary therapies only provide reduction in the severity of the disease, and there is an unmet need of efficient drugs. The present thesis provides a knowledge-based rationale to model MS disease mechanisms and identify potential drug candidates by using systems biology approaches. Systems biology is an emerging field which utilizes the computational methods to integrate datasets of various granularities and simulate the disease outcome. It provides a framework to model molecular dynamics with their precise interaction and contextual details. The proposed approaches were used to extract knowledge from literature by state of the art text mining technologies, integrate it with proprietary data using semantic platforms, and build different models (molecular interactions map, agent based models to simulate disease outcome, and MS disease progression model with respect to time). For better information representation, disease ontology was also developed and a methodology of automatic enrichment was derived. The models provide an insight into the disease, and several pathways were explored by combining the therapeutics and the disease-specific prescriptions. The approaches and models developed in this work resulted in the identification of novel drug candidates that are backed up by existing experimental and clinical knowledge