Building the Drug Safety Body of Knowledge: Safety Hypotheses and Information Sources in the Product Life Cycle; James Averback, President, Life Science Integration Partners

Recently, both the Pharmaceutical Industry and Regulators have been criticized for underestimating the need to fully understand and communicate the drug safety profile of a product before its use is promoted to maximize market share. Drug safety assessment is traditionally approached as a process of reducing the need to know about safety to fit within parameters required for a product's intended use and labeling as brought to market. As a consequence, new products have been exposed to withdrawal due to safety concerns which in turn has dimished the trust of patients in the industry. The cost due to liability of a withdrawn drug is high and trust takes a long time to win back. This talk proposes a strategy for proactively and continuously enhancing the body of safety knowledge relied upon by pharmaceutical companies and regulators to protect the public health and the bond of trust between them and patients.

Drug Safety Knowledge Management - Leveraging the Documentation of Safety Labeling Decisions; A. Leander Fontaine, M.D., President, Pharmiceutics LLC

Safety labeling decisions, whether for core labeling or local labeling, capture the outcome of all discussions on a possible duty to warn about a definite or suspected risk. Such decisions may determine a possible risk as to be included in labeling, or as insufficiently substantiated for inclusion. The need to provide special advice to users, and the type of advice (e.g. contraindications, precautions) are subject to labeling decisions as well. Labeling decisions are also made to accept or refute requests by regulatory authorities to modify labeling.

Core labeling (e.g. in the form of Company Core Data Sheets or Core Safety Information contained in Investigator's Brochures) does not reflect the full spectrum of safety labeling decisions made. It does typically not mention risks and warnings that were not considered "label-worthy", nor does it typically contain "retired items". It can therefore usually not be considered to be a sufficient reference point for finding a company's position on all safety topics that ever reached the stage of formal labeling considerations.

A complete picture can often only be obtained by reviewing all labeling decisions for a product. Electronically searchable inventory lists of labeling decisions can be helpful in performing this task.

Much more powerful is a database that contains an elementarized representation of core labeling content, local labeling elements that have not been accepted for core labeling, retired or rejected items, and topics under labeling discussion. Such a database can form the kernel of a Drug Safety Knowledge Management System, by linking to, e.g.,
- supporting documentation (rationales, reports, data, etc.)
- administrative information (decision records, etc.)
- tracking and audit information (implementation milestones, reasons for local deviations, need for action, etc.)
- safety databases and electronic reporting systems.

The content of such a "Labeling Decision Register" can also be linked to text sections and coded content in structured product labeling in the US (SPL), EU (PIM) and in other countries with structured labeling in XML format.

The granularity of elements in the register will depend on pragmatic considerations (granularity needs for decision recording and tracking, etc.) and will have its maximum in the adverse reactions section. The register may also capture MedDRA codes (increasing its searchability) and map possible future MedDRA group terms to PTs.

Designing and Managing a Risk Management Tracking Program; John Clark, Vice President of Surveillance Services, Galt Associates

The FDA recently released guidance documents for the development of risk management plans. One important component of any risk management plan that is not discussed by these guidance documents is the tracking/monitoring of program impact. The tracking of adverse event report data associated with a marketed product can be a daunting task, especially since such programs often require technologies that plot AE data over both time and geographical location. In addition, summaries of both prescribers and patients are frequently requested components. This presentation will present the logistical difficulties one must take into consideration when developing tracking/monitoring programs, will discuss general strategies for meeting these challenges, and will describe pertinent automated methods. The presentation will use the publicly available AERS database to illustrate these points. Finally, the role of the tracking/monitoring module to its overall risk management program will be discussed in the context of risk:benefit balance.

We must build the Knowledge Management Body of Knowledge (KMBOKâ„¢); Douglas Weidner, President, KM Institute

We must move successfully into the Knowledge Age. To do that, we must master the discipline that has come to be called Knowledge Management (KM) and create a KM Body of Knowledge (KMBOKâ„¢) that is so essential to the success of KM and its practitioners. Without a KMBOK as an enabler, we will not adequately document for use proven solutions, methodologies, and best practices, nor understand the roles and competencies needed for both KM leadership and knowledge worker productivity in the Knowledge Age. Most importantly, we will not have the robust core content for the requisite KM Learning curriculum.

Here's what the KMBOK must contain:

Methodology - KM is a Strategic Initiative; the methodology must be strategic, not tactical. But, to be useful it must be far more robust than a list of preferred phases or steps. Most methods today are not sufficiently descriptive, and are mere guidance rather than useful.

Curriculum - Learning involves specifying the requisite KM roles, competencies and learning objectives to enable them, not just a KM course for the sake of a course. Few KM courses are competency-based because of difficulty defining KM competencies. The KMBOK must define roles, competencies, and learning objectives.

Proven Solution Providers - Much KM is enabled by technology, but which ones work and solve real needs must be known and available for testing.

Knowledge Repository - Finally, all the above depends on having a repository of the latest thought, best practices, lessons learned, etc. Many sources attempt this, including hundreds if not thousands of links.

This talk focuses on modern Knowledge Repositories. The KMBOK can't be just a repository of KM links. It must be technology-enriched in all KM domains/specialty areas, including intelligent agents doing searches, ability to summarize documents based on your profile, and the ability to navigate across documents by contexts, not just terms.

Capturing and Managing Research Records to support Drug Safety Knowledge Networks; Jeff Spitzner, Chief Science Officer, Rescentris

The effective practice of personalized medicine must transform drug development life cycles from a linear process into a network of feedback and interplay among knowledge systems for R&D, clinical trials, and market data. Drug safety data will be continuously re-analyzed and re-evaluated in light of new biomarkers, pathways, genomics, proteomics, and other data coming from upstream activities. Likewise, new research information will be applied downstream to guide patient selection for clinical trials and drug treatments. Creating effective drug safety knowledge networks requires overcoming a large number of barriers. This presentation will focus on key issues for capturing and integrating research data to support the feeding and harvesting of research knowledge systems that can facilitate the safe and effective use of drugs. These issues include:

1. Overview of the information products generated by research, and systems to manage them.
2. Capturing complete research records - documents, data, metadata, record-keeping information.
3. Three types of repositories used for every experiment - data-centric, people-centric, process-centric - and how they can be bridged by knowledge networks.
4. Three dimensions of collaboration and integration - vertical (the org. chart), horizontal (cross-discipline), and time axis (product development life cycle).
5. Use of standards and ontologies to connect and relate complex content, including capture of scientific evidence and interpretation.
6. Other issues for capturing and managing research records while meeting needs of enterprise stakeholders: science, business/R&D management, IT, and legal/regulatory.

Personalized Medicine - integration of bioinformatics and medical informatics for safer and more efficacious healthcare practice and medicine; Professor Peter L. Elkin, MD, Mayo Clinic, College of Medicine

Personalized Medicine is the integration of genotypic, proteomic and metabolomic data with phenotypic data in support of ordering just the right drug for the correct patient with a specific disease. As we move toward an era of personalized medicine which is driven by an understanding of each individuals genetic fingerprint and their evolving gene and protein expression, we provide an infrastructure ready to support a safer and more efficacious practice of medicine. With patients at the center of our paradigm of care we invert the current healthcare practice environment placing once again the emphasis on the needs of the patient. Dr. Elkin firmly plants us in the present and then leads us into a journey into the future where safer more efficacious practice of healthcare is coupled with an environment that generates new knowledge more rapidly and applies that knowledge at the bedside.

The Drug Development Process of the Future; Gene Odle, Founder, eValueDrugs

Imagine:
· A world with fully integrated systems where the people who receive healthcare and those who deliver it have access to the right information, at the right time, on the right device, presented in the right way.
· A world where everyone carries his medical history and genetic profile on a digital device and manages his well-being based on one's specific genotype and phenotype rather than waiting to treat a disease.
· A world based on personalized medicine through leveraging a comprehensive approach for integrating all available data & information to provide actionable knowledge with invaluable insight.

This vision is at the foundation of eValueDrugs and drives the core development for business tools, techniques and know-how to deliver a complete data integration process based on innovative integrated electronic solutions.

eValueDrugs focus starts with today's highly inefficient and costly drug development process. The Pharmaceutical industry faces daunting hurdles in bringing new products to the market. It is common knowledge that out of 10,000 drug candidates only one will be brought to the market at an average cost of $800 million to $900 million over 12 to 14 years. The highest attrition rates with the majority of the cost and time spent is found in the development phases of the overall drug development process and it is here where eValueDrugs is building its comprehensive process integration platform for dramatically reducing these costs & time.

A Changing Paradigm

Closer collaboration: In today's healthcare network a much greater co-operation between the various participants is a clear requirement. However, forming such collaboration is difficult and there are several practical problems, including the fact that most pharmaceutical companies use bespoke systems for managing their drug development processes in order to compile their data and changing these systems would be prohibitively expensive. But one way of overcoming this dilemma is to use a trusted third party like eValueDrugs that spans the gap and acts as the bridge linking all participants into one comprehensive integration process.

Revolutionizing the entire Drug Life Cycle

Through aggregating the multiple data collection streams between bio-pharmaceutical companies and all other constituents in the drug development process, eValueDrugs orchestrates and coordinates in real-time the multitude of different data and information streams, thereby turning the data into actionable knowledge and invaluable insight for all parties concerned.

Symyx IntelliChem's iELN: Meeting the Needs of Intellectual Property; Ronald A. Krasnow, Esq., Vice President of Intellectual Property, Symyx Technologies, Inc., and Scott K. Starry, Senior Project Manager, Symyx IntelliChem

Without a doubt, the IntelliChem iELN makes an IP lawyer's job easier, particularly on a day-to-day basis. The information is stored and accessible in typed, uniform formats, meaning that lawyers do not have to interpret poorly-drafted, hard-to-read handwriting. Also, the information is directly available to the lawyer through the IntellIChem iELN search methods, which patent lawyers can use to find data to support patent applications. There are nine different ways to search for data, so lawyers are no longer required to sift through notebooks of group members who might have worked on a project to find co-inventors or other data.

Another concern of some patent lawyers is uniformity of lab notebook policy adherence. The IntelliChem iELN can reduce this concern through workflow controls that encourage policy adherence, e.g., effectively reducing or eliminating the sometimes common practice of bulk witnessing of documents years after an experiment is completed. The uniform notebook format minimizes the likelihood of incomplete or lost information, and the data can be stored for years and years in a format consistent with corporate policy.

IP lawyers may be concerned about electronic lab notebook data being admissible in court and/or whether electronic data will be convincing to a judge or jury. There are many issues wrapped in these two concerns, and the bulk of this presentation addresses these issues. As a summary, IntelliChem iELN records are as admissible and convincing in court as any other electronic data (e.g., e-mail). For example, the IntelliChem iELN has an easy-to-explain software architecture, which was created in a structured environment. This makes it easy for jurors to understand the reliability of the system. Lawyers can assist in the admissibility and cogency of the IntelliChem iELN data by enacting smart corporate policies and insisting on adherence to those policies.

Lastly, this presentation will consider how to roll out an intelligent lab notebook system in a corporate environment. The procedure is straightforward but suggests participation by a lawyer to assure that the process is competently completed in a manner approved by the legal department.

Aggregation of Relevant Clinical and Non-clinical Drug Safety Information from Multiple Sources of Unstructured Data; Jim Walker, Jeffrey Wolff and David Phillips, Corpora

Modern knowledge workers have access to unlimited documentation, but they struggle to locate highly relevant text and lack sufficient time to read all pertinent documents fully. There is an unmet need in the process of internalizing drug safety information and a requirement to proactively manage risk related to the use of modern drug therapies. Corpora is currently evaluating the application of its solutions to effectively and automatically aggregate relevant clinical and non-clinical drug safety information from multiple sources of unstructured data.

The capability of Corpora tools will be outlined in the context of solving the clustering of Adverse Event Reactions, accessing public data, pointing to and indexing internal data in order to better understand what has been done and the decision process that supports fundamental decisions, with regard to drug safety.

The Corpora solution includes a process of event clustering, spidering and indexing data sources, providing concept search capability, all using linguistic technologies to return accurate, medically relevant, high value information. When the agents return documents of interest, Summarize! provides a fast, tailored, configurable summary for quick review. Jump! is then used to create a workspace with multiple documents of varying formats - Word, PDF, HTML, Text, etc. The power of Jump! is best achieved when navigating to terms and concepts of interest, across many documents and linking directly to the context of how the terms appear in the documents.

Corpora believes that KM software providers must move beyond simplistic word search systems to create software that understands unstructured text documents.

Bridging the Gaps: Integrating Systems to improve Drug Safety; Jim Cook, Director, Volutio Ltd

This presentation focuses on two aspects of the drug safety problem. Attendees will gain valuable perspectives on two areas in the typical Life Sciences organisation that can benefit from new approaches to drug safety. Firstly, the talk will explore the problems associated with disparate data repositories and business processes currently prevalent in the Life Sciences arena. Secondly, the presentation will examine the type of knowledge management issues presented by the drug safety problem space. Finally, the talk will present a consolidated view of typical components to the solution.

Ontologies for Pharma; Sheryl Torr-Brown, Head of Knowledge Management & Technology, World-Wide Safety Sciences, Pfizer

There are two givens in the pharmaceutical industry today. Firstly, we can now generate an unprecedented amount of drug related information along the Research and Development (R&D) pipeline, and secondly, we are more connected to each other than we have ever been through the internet revolution of the past 15 years or so. Both of these aspects of the modern pharmaceutical company have brought many benefits to our business. However, the pharmaceutical industry is currently under fire due to allegations of decreased productivity despite significant investments in R&D, that if left to continue at this pace, will reach almost $60 billion by 2006. The concept of Ontology and it relevance to a new model of knowledge management is discussed in the presentation. It is argued that systematic knowledge management will be increasingly necessary in order to optimize the value of preceding advances in high throughput approaches to research and development, and to fully realize the anticipated increase in productivity.

Knowledge Management in Drug Safety; Sidney N Kahn, President, PvRM, Inc.

The global drug development climate has undergone dramatic changes during the past decade, and the pace of change shows no sign of decreasing. At this crucial time, when the need for effective and safe innovative medicines has never been greater (e.g. emergence of new infectious agents, increasing microbial antibiotic resistance, unmet health needs in the developing world, and large aging populations in developed regions), advances in basic science and technology carry the promise of remarkable therapeutic advances. However, while pharmaceutical companies spend vast sums on R&D, the number of new molecular entities licensed appears to be steadily diminishing. Simultaneously, a recent series of high profile drug withdrawals due to significant safety issues has reduced the confidence of health professionals and the public in both the current development process and the regulatory procedures that are intended to ensure the safety of pharmaceutical products, and caused significant financial harm to their developers. While it is unrealistic to expect very rare undesired outcomes to be detectable during development, effective application of knowledge management tools for integrating information from a variety of sources could result in earlier detection and mitigation of risks attributable to newly-marketed medicines and thus possibly prevent the withdrawal of useful products from the market.

This presentation discusses those areas of pharmacovigilance in which Knowledge Management tools may be of greatest use in preventing unexpected and untoward safety outcomes.