Key challenges in Pharmacovigilance

Challenge: how to standardize processes and data management Development of a common platform across different geographic locations, functional groups, product lines. Integration of data — a single database to include data across the entire product life cycle (pre and post- market). Challenge: multiple databases may contain similar information but are not linked/linkable to each other. Implementation of work flow management technology — identify and distribute information to stakeholders according to a predetermined set of rules. Ensure only the appropriate employees receive the data required to inform the decisions they are authorized to make. “We don’t view drug safety from a postmarket or premarket perspective but, rather, as a continuum from the time the compound is identified and the time of animal studies on through when companies are hoping to get approval...” Alan Goldhammer, Associate vice president of regulatory affairs for the Pharmaceutical Research and Manufacturers of America (PhRMA) (source: PWC report)

Challenge: Implement proactive risk management Development of a risk management action plan — establish risk scoring and mitigation processes to evaluate external risk factors (regulatory, reputation, product liability) and internal (portfolio, strategic and financial risk). Implementation of data mining techniques — assess the patterns, time trends and events associated with drug-drug interactions. Dashboard — summarize safety information across the product portfolio in real time. Identify the types of data that should/should not be used in drug safety decision making.

Challenge: run PV operations cost effectively Growing amount of data causes important safety signals to be missed — how to deal with the data storm? Outsourcing may be done at product level resulting in mixed vendors and models. Signal identification must not be lost due to segmentation of the analysis by different parties. Embase, October 2014 ‘Cost savings of 30–40% can be achieved through outsourced pharmacovigilance activity’ http://www.pmlive.com/pharma_news/outsourcing_phar macovigilance_352870

Addressing the challenges in pharmacovigilance

Our mission in pharmacovigilance Elsevier provides the capabilities necessary for Pharmacovigilance and Drug Safety groups to be more efficient, stay compliant and mitigate risk

our framework 1) Avoid missing critical information Automated Literature Triage Integration with case reporting systems and audit trails Automated Literature Monitoring Regulatory Data for Risk Mitigation Strategies Output Analysis Case Input Case Processing Case Output 2) Save time with better article pipeline management 3) Connect literature to broader ecosystem 4) Manage risk of late-stage failure

Percentage of relevant articles retrieved Effort / tools required Embase The world’s most comprehensive biomedical research tool Percentage of relevant articles retrieved 0 % 50 % 100 % Effort / tools required GOOGLE EMBASE PUBMED SOURCE SCOPUS TEXT MINING Reliable and authoritative content to help the drug and drug-related research community advance new biomedical and pharmaceutical discoveries. Confidence Find all relevant articles that may not otherwise be found by using alternative databases Deep Biomedical Indexing All relevant, up-to-date, biomedical information from the research literature Precise Retrieval Deep and focused research using the most powerful retrieval tools

Embase vs. Medline (content) Includes all Medline content plus much more Over 2600 journals not indexed on MEDLINE, especially from countries outside North America Over 300,000 conference abstracts from 1000 conferences each year (since 2009) In-depth drug and medical device indexing based on the Emtree Life Science thesaurus, which has over twice as many terms as the PubMed (MEDLINE) thesaurus (MeSH) Embase Unique Embase & Medline Medline on Embase 5.9m 2600 11.8m 3000 8.3m 2500 EMBASE A&G 101 SALES TRAINING, MARCH 2014

Biomedical Scope and coverage extensive coverage of peer-reviewed biomedical literature Pharmacology & Taxicology 12% General Clinical Medicine 11% Genetics, Biochemistry & Molecular Biology 10% Neurology & Behavioral Medicine 8% Microbiology & Infectious Disease 7% Cardiology & Hematology 6% Psychiatry & Mental Health 6% Oncology 5% Healthcare Policy & Management 4% Allergy & Immunology 4% Pediatrics 4% Endocrinology & Metabolism 3% Obstetrics & Gynecology 3% Biomedical Engineering & Medical Devices 3% Anesthesiology & Intensive Care 3% Gastroenterology 2% Respiratory Medicine 2% Nephrology & Urology 2% Dermatology 2% Other topics 28% Including public health, basic biomedical science and topics included from MEDLINE EMBASE A&G 101 SALES TRAINING, MARCH 2014

quosa Improving biomedical literature search and risk monitoring A combination of software and services that allows customers to reduce risk, remain compliant and ensure that workgroups have the latest scientific literature Pharmacovigilance — Monitor literature for adverse drug events Medical Affairs — Collect and share the latest information for Key Opinion Leaders and healthcare providers Medical Devices — Conduct post- market surveillance for adverse events reporting and pre-market approval Information Management — Collect, organize and share key documents for your stakeholders 12

Sanofi adopted quosa and embase for their literature review October 22, 2013 Elsevier, a world-leading provider of scientific, technical and medical information products and services, today announced that Sanofi, one of the world's leading pharmaceutical organizations, has implemented QUOSA's literature management tools to automate adverse event monitoring.  Users: Information managers, CRO, Pharmacovigilance (PV) Challenges: Existing systems for alerts and content management were not efficient or scalable Under threat from the regulator

Embase & Pharmapendium Improving biomedical literature search and risk monitoring A single drug search in Embase seamlessly links to PharmaPendium to deliver: Comprehensive information that better informs a risk management / pharmacovigilance strategy Drug safety information reported in the literature FDA/EMA approval and drug review reports that provides insights into historical regulatory precedents A direct link to preclinical and clinical observations and reported adverse events (AERs) to better monitor and anticipate safety risks 14

+ Embase + Quosa: AUTOMATING POST-MARKET literature SURVEILLANCE 1 2 3 An information specialist develops a comprehensive search strategy for a drug in Embase The search strategy is tested, validated and regularly maintained (at least 3 times a year) The information manager sets up a daily or weekly alert containing the search strategy Alert results are automatically loaded into QUOSA, deduplicated, full-text retrieved and stored in specified folders Quosa enables further annotation and indexing, ‘internal alerts’ and text analytics PV / regulatory specialists receive only relevant full text, annotated and deduplicated, pre-analyzed full text records to review 4 5 6 +

QUOSA Software and Services Online literature databases ELSS Pharmacovigilance Solution Summary QUOSA Software and Services PSURs Online literature databases Review and annotate articles from a scalable central library Receive alerts to rapidly identify adverse events in literature Use pre-formatted output to easily create reports ICSRs Conference Documents Other Safety and Compliance Reports Journal RSS Feeds ELSS SERVICES: Set up advice, consultancy on potential for text mining

Text Mining & Data Integration Out of 10,000 compounds considered or studied only 1 will be approved by the FDA and/or EMA (regulatory authorities) as a new drug It is important to increase the probability of selecting a lead = successful candidate drug early in the R&D value chain (before large scale clinical trials) This highlights the importance of information decision solutions and the value ELSS portfolio of products to our customers Text Mining & Data Integration