Pharmacogenomics (PGx) studies how individual gene variations cause variability in drug responses. A state of the art of PGx is available and constitutes a basis for implementing personalized medicine, i.e., a medicine tailored to each patient by considering in particular her/his genomic context. However, most of the state of the art of this domain is not yet validated, consequently not yet applicable to medicine. Indeed, most of it results from assays that do not fulfill statistics validation standards and are difficult to reproduce because of the rarity of gene variations studied (making hard to recruit sufficiently large cohorts) and of the multifactorial aspect of drug responses. Beside, the generalizing use of Electronic Health Records (or EHRs) generates large repositories that offer new opportunities such as composing patient cohorts for the study of clinical hypotheses hard to test experimentally. Typically, EHR repositories make possible to assemble cohorts of patients to study, on the basis of practice-based data, the impact of gene variations on drug responses. The goal of the PractiKPharma project (Practice-based evidences for actioning Knowledge in Pharmacogenomics) is to validate or moderate PGx state-of-the-art (SOTA) knowledge on the basis of practice-based evidences, i.e., knowledge extracted from EHRs. Units of knowledge in PGx typically have the form of ternary relationships gene variant–drug–adverse event, and can be formalized to different extents using biomedical ontologies. To achieve our goal, we propose: (1) to extract SOTA knowledge from PGx databases and literature, (2) to extract observational knowledge (i.e., knowledge extracted from observational data) from EHRs, (3) to compare knowledge units extracted from these two origins, to confirm or moderate SOTA knowledge, with the ultimate goal of enabling personalized medicine. (4) Finally, we intend to emphasize confirmed knowledge by investigating omics databases for molecular mechanisms that underlie and explain drug adverse events. For this investigation will use and contribute to the biomedical Linked Open Data. The PractiKPharma project involves a multidisciplinary consortium of 4 academic partners: 2 informatics experts, the LORIA of Nancy (coordinator), the LIRMM of Montpellier; and 2 biomedical experts, the HEGP (Paris) specialized in EHRs management and PGx, and the SSPIM (from CHU Saint-Etienne) specialized in medical informatics and pharmacovigilance. The expected impacts of PractiKPharma both in computer science and in its application domain are: novel methods for knowledge extraction from text and EHRs; multilingual semantic annotation of EHRs; methods for representing and comparing SOTA and observational knowledge; a database that maps genotypes to quantitative traits to facilitate the study of PGx with EHRs; the completion and connection of Linked Open Data related to PGx; methods for hypothesizing on mechanisms of adverse events; validated PGx knowledge units. Consequently, our ultimate goal is to provide clinicians with actionable PGx knowledge to establish guidelines that, implemented in personalized medicine, will reduce drug adverse events, and then improve the quality of clinical care.

Providing new technologies to access data implies to reconcile, on one hand, the expressivity of formal query languages and, on the other hand, the usability of these tools for the end user. For example, SQL is admitted as a query language in the majority of relational databases, but it suffers from an insufficient level of conviviality for an end user who is not familiar with databases. Therefore, interfaces are developed to improve the usability of data-access methods and to conceal the difficulties related to technical languages. Unfortunately, end user interfaces often limit the access to the full expressivity of these languages. Recently, rapid growth of the semantic Web and of linked open data introduced a new paradigm for data accessibility, which allows requesting data in a more efficient way. But using formal languages such as SPARQL is difficult for non-specialist staff, and requires understanding the RDF resource, which is an additional difficulty for the user. In order to improve the access to semantic resources, interfaces were proposed, but the proof that such interfaces improve user experience still needs to be established. Pharmacovigilance is the activity related to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. The Adverse Drug Reactions (ADRs) are coded in pharmacovigilance databases using the MedDRA (Medical Dictionary for Regulatory Activities) terminology. In France, in the public sector, health professionals and patients can spontaneously report ADRs to regional pharmacovigilance centers (CRPV) which register these cases in the French pharmacovigilance database. Some partners of the project have already developed a semantic resource, OntoADR which allows querying MedDRA using formal languages, but this query method was unattainable for pharmacoviglants. The hypothesis of the PEGASE project (Pharmacovigilance Enrichie par des Groupements Améliorant la détection des Signaux Émergents) is that interfaces with better usability level will allow to enhance user experience whilst preserving the high expressivity of formal queries. To query OntoADR, several types of interfaces will be evaluated. We will consider interfaces based on forms, on graphs, or on natural language. In addition, interfaces based on the VMC (Visualization of medical concepts) iconic language, and visualization with rainbow boxes will be developed and evaluated. A particularity of the project is to propose, throughout the development of prototypes, a user-centered approach. The design of this approach will take into account the cognitive process of the pharmacovigilance activity. The prototypes will be developed by following the principles of agile software development, including several cycles of ergonomic evaluation, allowing the improvement of the usability of the prototypes. A final evaluation of the usability will involve pharmacovigilance experts. The project is coordinated by the Unit of Public Health and Medical Informatics of the CHU University Hospital of Saint Etienne and envolves another laboratory of medical informatics, INSERM U1142 LIMICS. The LIS team of IRISA will adapt its tool SPAKLIS for the purposes of the project. CIC-IT Evalab, an ergonomics laboratory, will lead the usability studies of developed prototypes in connection with end users. These end users are the pharmacovigilants of CRPV (Besançon, Lille, Paris HEGP and Toulouse), who will be also responsible of the evaluation on their activities, especially for querying case reports in the French pharmacovigilance database and for statistical signal detection.