Improving drug safety: From adverse drug reaction knowledge discovery to clinical implementation

Abstract

Adverse drug reactions (ADRs) are a major public health concern, causing over 100,000 fatalities in the United States every year with an annual cost of $136 billion. Early detection and accurate prediction of ADRs is thus vital for drug development and patient safety. Multiple scientific disciplines, namely pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing the ADR problem from different perspectives. With the same goal of improving drug safety, this article summarizes and links the research efforts in the multiple disciplines into a single framework from comprehensive understanding of the interactions between drugs and biological system and the identification of genetic and phenotypic predispositions of patients susceptible to higher ADR risks and finally to the current state of implementation of medication-related decision support systems. We start by describing available computational resources for building drug-target interaction networks with biological annotations, which provides a fundamental knowledge for ADR prediction. Databases are classified by functions to help users in selection. Post-marketing surveillance is then introduced where data-driven approach can not only enhance the prediction accuracy of ADRs but also enables the discovery of genetic and phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR requires well organized patient genetics information and analysis by pharmacogenomic approaches. Finally, current state of clinical decision support systems is presented and described how clinicians can be assisted with the integrated knowledgebase to minimize the risk of ADR. This review ends with a discussion of existing challenges in each of disciplines with potential solutions and future directions.

Serotonin Syndrome after Initiation of Pregabalin on a Stable Regimen of Antidepressant Medication

“…Consequently, increasing research efforts have been initiated in order to enhance the knowledge on adverse drug reactions, including clinical decision support systems, databases on drug-target interactions and drug-drug interactions, as well as pharmacogenomic approaches (see [16] for a recent overview).…”

Advances in Clinical Decision Support: Highlights of Practice and the Literature 2015-2016

“…For example, work to detect and even predict adverse drug reactions can help to improve quality by reducing the negative consequences of clinical care [36]. Automated techniques for knowledge discovery that can inform CDS work to improve medication safety also emphasize quality improvement [37]. Additional work in this area shows how the use of patient data coupled with CDS that detects early clinical deterioration in, for example, the pediatric inpatient setting, including the use of patient dashboards to inform treatment that intervenes before serious deterioration, may improve the quality of care [38].…”

Analysis of Gene‐Gene Interactions

“…Structural studies of genetic variation within the genomes of populations of humans have established thresholds for rejection of the null hypothesis of no association (Sham & Purcell 2014 large populations of unrelated humans. GWAS has discovered statistically significant associations between genetic variants and human traits, including disease susceptibility (Welter et al, 2014) and medication contraindication (Stankov, Sabo, & Mikov, 2013;Tan et al, 2016), that promise to revolutionize the practice of medicine through genomic precision.…”