Pharmacovigilance the OTHER discovery process in Pharma Daniel Mayer, Product Marketing Manager...

Pharmacovigilancethe OTHER discovery process in Pharma

Daniel Mayer, Product Marketing ManagerOlivier Feller, Life Sciences Consultant

7th Text Mining SymposiumOct 5-6th 2009

Copyright © 2009 TEMIS - All Rights Reserved - Slide 2

Agenda

A process view of safety in pharma Why is pharmacovigilance necessary ?

• Clinical Trials have key benefits but also some limits• But how important and urgent is this issue ? • Where does pharmacovigilance fit in the process ?

A new definition of Pharmacovigilance What role does Text Mining play in Pharmacovigilance ? How is Luxid® used for this purpose ?


The Safety Process In Pharmaceuticals

Prevent harmto patients

Prescribethe right dosageof the right drugto the right patient

Rigorously screenClinical Trial Reports

OptimizeDrug Labellingfor available drugs

HealthcareProviders

Regulatory Authorities

Pharmacompanies

PerformClinical Trials

Removelow b/h ratio drugsfrom the marketas soon as possible


Agenda


• Benefits and Limits of Clinical Trials• Importance and Urgency• Where does it fit in the process ?

A new definition of Pharmacovigilance What role does Text Mining play in Pharmacovigilance ? How is Luxid® used for this purpose ?


Benefits and Limitations of Clinical Trials

Clinical Trials proove with some certainty that the product is effective and identify the common serious adverse events but have limitations




Relatively Homogeneous populations• Relatively healthy patients with only one disease• Patients with complicated medical conditions often excluded• Not sufficiently ethnically diverse • Specific groups such as pregnant women, children, and elderly

people are mostly excluded




Relatively Homogeneous populations Small sample size

• rarely more than 3000 patients• reduces the chance of finding rare adverse effects




Relatively Homogeneous populations Small sample size Limited duration

• long term consequences such as cancer cannot be discovered




Relatively Homogeneous populations Small sample size Limited duration Difficulty to predict the real world

• Patients receiving certain concurrent drugs are often excluded• Drug interactions can therefore almost never be predicted from

clinical trials, even though they may be substantial• Food-drug interactions are also not covered




Relatively Homogeneous populations Small sample size Limited duration Difficulty to predict the real world

… but how urgent and important is it to address this issue ?


Quantifying The Costs Of Adverse Drug Reactions

Approximately 5% of all hospital admissions are caused by ADRs• 2% of these admitted patients die• 4% of hospital capacity• 72% avoidable




Direct costs in US estimated at US$ 130 Billion annually




Direct costs in US estimated at US$ 130 Billion annually Drug-related litigation costs Pharmas Billions




Direct costs in US estimated at US$ 130 Billion annually Drug-related litigation costs Pharmas Billions

The faster you address a problem the better


Alternative definition of Pharmacovigilance

It is important and urgent to put in place a process that completes Clinical Trials




Post-marketing monitoring for safety [FDA] Detection, assessment, understanding and prevention of Adverse

Drug Reactions (ADRs), particularly long-term and short-term side effects of medicines [WHO]




Post-marketing monitoring for safety [FDA] Detection, assessment, understanding and prevention of Adverse

Drug Reactions (ADRs), particularly long-term and short-term side effects of medicines [WHO]

A discovery process focused on contra-indications linked to• Specific therapies• Specific populations• Specific interactions


Where does Pharmacovigilance fit ?

Prevent harmto patients

Prescribethe right dosageof the right drugto the right patient

Rigorously screenClinical Trial Reports

OptimizeDrug Labellingfor available drugs

HealthcareProviders

Regulatory Authorities

Pharmacompanies

PerformClinical Trials

Removelow b/h ratio drugsfrom the marketas soon as possible

Understand and qualifyunexpected ADRsas fast as possible

Report unexpected ADRs

MinimizeSocial cost

Minimizeliabilities


Agenda



A new definition of Pharmacovigilance Why Text Mining in Pharmacovigilance ? How is Luxid® used for this purpose ?


Why Text Mining For Pharmacovigilance ?

Enables unified access to many heterogeneous sources• Doctor/Pharmacist reports• Medwatch / AFSSAPS / NIMH• Consumer Forums• Call center transcripts• Summary of Product Characteristics• Scientific literature (Pubmed)• Some structured databases• Regulatory authorities reports and Approval packages• Internal documents



Enables unified access to many heterogeneous sources Enables information discovery even though a large part of the

content is unstructured• Including relations between disorder, treatment, population, ADR




content is unstructured Helps to contextualize new information

• Link new information to other sources• Gain insight into the bigger picture




content is unstructured Helps to contextualize new information Accelerates the contraindication discovery process





Enables faster response time to unexpected ADRs• Investigation / Qualification of ADR cases• Relabelling• Recall





Enables faster response time to unexpected ADRs Reduces public exposure to potentially serious ADRs





Enables faster response time to unexpected ADRs Reduces public exposure to potentially serious ADRs Minimizes social and corporate risk


What typical Pharmacovigilance questions does Text Mining need to address ?

Which unexpected ADRs have been reported for this drug ?

Which populations have been exposed to unexpected ADRs ? • Age• Ethnic characteristics

Which treatment caused ADRs ?• Dosages, Duration, Frequency, Administration Route• For which Indication

What was tested during the Clinical Trials ?


Agenda



A new definition of Pharmacovigilance Why Text Mining in Pharmacovigilance ? How is Luxid® used for this purpose ?


Front-end

Luxid® Annotation Factory

Luxid® platform overview

Luxid® Productivity Tools

Knowledge Mgr

Skill Cartridge Mgr

Luxid® Content Pipeline

Back-end

webservice

Luxid® Toolbar

Luxid® SkillCartridgeTM Library

Luxid®Information Analytics

Copyright © 2009 TEMIS - All Rights Reserved - Slide 31Copyright © 2009 TEMIS - All Rights Reserved Slide 31

Overview - The "Vigitermes" Project

A research project from the National Research Agency The purpose is to build a global platform dedicated to

pharmacovigilance A dedicated Skill Cartridge™ has been developed

based on the "Medical Entity Relationship" Skill Cartridge™


Pharmacovigilance sentence samples - Entities

The authors report 2 cases of hepatocellular tumour in children treated with anabolic androgens for aplastic anemia.

A 10 year old girl with HCV infection was treated with Ribavirin for 12 months at 1,2 mg/day and developed anemia.

We report a 41-year-old female, treated with etanercept for a rheumatoid arthritis, who developed a cutaneous lupus.

A 32-year-old woman was treated for severe aplastic anemia with norethandrolone over a period of 4 years, with a cumulative dose of 25 g.

Legend:

Patient Symptom Drug Disorder Drug Usage


Pharmacovigilance sentence samples - Relations

The authors report 2 cases of hepatocellular tumour in children treated with anabolic androgens for aplastic anemia.

A 10 year old girl with HCV infection was treated with Ribavirin for 12 months at 1,2 mg/day and developed anemia.

We report a 41-year-old female, treated with etanercept for a rheumatoid arthritis, who developed a cutaneous lupus.

A 32-year-old woman was treated for severe aplastic anemia with norethandrolone over a period of 4 years, with a cumulative dose of 25 g.

"Therapy" relationships "Patient with Disease" relationships


Enrich existing concepts (drug, adverse effect) - Lexicons

Theriaque• A database of all drugs available in France containing official regulatory information

and validated bibliographic information Thesorimed

• Another database of all drugs available in France MedDRA (Medical Dictionary for Regulatory Activities)

• A clinically validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry

RX Norm• Normalized names for clinical drugs with links to many commonly used drug

vocabularies (First Databank, Micromedex, MediSpan, Gold Standard Alchemy and Multum)

Drug Bank• Unique bioinformatics and cheminformatics resource that combines detailed drug

(chemical, pharmacological and pharmaceutical data) with comprehensive drug target (sequence, structure and pathway information)


Data sources involved

Scientific Literature (PubMed) Pharmacovigilance Reports Summary of Product Characteristics (SPC) Meyler's Side Effects of Drugs (The International Encyclopedia of

Adverse Drug Reactions and Interactions) Doctor/Pharmacist reports MedWatch / AFSSAPS reports Regulatory authorities reports and EMEA/FDA approval packages …


Cells and Tissues Clinical Trials Diagnostic Methods Diseases Enzymes Patients

• Age• Ethnic Origin

Treatments• Drug Dose• Drug Duration• Drug Frequency• Administration Route

Symptoms

Extracted Entities


Cell Disease• Relationships between Cells and Tissues, Symptoms and Disorders

Cell Diagnostic Methods• Relationships between Cells and Tissues and Diagnostic Methods

Cell Treatment• Relationships between Cells and Tissues and Treatments

Clinical Research• Relationships between Clinical Trials, Disorders, Patients

Diagnosis• Relationships between Disorders, Diagnostic Methods, Cells and Tissues and patients

Patients with Disease• Relationships between Patients and Disease

Therapy• Relationships between Disorders, Treatments, Symptoms and Patients

Treatment Effects• A negative effect of a treatment in relation with Symptoms, Disorders and patients• A treatment without effect or with a neutral one in relation with Symptoms, Disorders and

patients• A positive effect of a treatment in relation with Symptoms, Disorders and patients

Extracted Relationships


Extraction overview in IDE Demo Client

Therapy (relationship)

Dosage- Frequency- Administration- Dose- Duration

Treatment- External (from lexicon)

Living Being- Age- Ethnic Origin- Gender

Disease- MeSH disease


Therapy relationship example

Dosage: Frequency, Administration

Therapy (Relationship)

Dosage: Dose, Duration

Treatment: External (from lexicon)

Disease: MeSH disease

Living Being- Age- Ethnic Origin- Gender

Daily oral Capsaicin at 3 mg/kg for 1 year administered to 60 year old Chinese men to regulate hay fever.


Entities’ hierarchy

Dosage- Administration- Dose- Duration- Frequency

Treatment- External (from lexicon)

Disease: MeSH disease

Living Being- Ethnic Origin- Gender

Living Being: Age

Treatment - External (from lexicon)

Daily oral Capsaicin at 3 mg/kg for 1 year administered to 60 year old Chinese men to regulate hay fever.


Relationship hierarchy (Therapy example)

Therapy (Relationship)

Treatment

Living Being

A Therapy Relationship is based on a Treatment and a Patient


Overview of potential relationships


Links between an Symptom, a Patientand a Treatment

Dosage

Patient

Symptom


Links between entities and attributes (1/2)

Dosage

Prevalence

Patient

Inheritance

Entities Attributes


Links between entities and attributes (2/2)Dosage

Patient

Prevalence

Inheritance


Clinical Research - Entities involved

Clinical trial

Patient

Disorder


Agenda



A new definition of Pharmacovigilance Why Text Mining in Pharmacovigilance ? How is Luxid® used for this purpose ? Conclusion


Value Proposition in Pharmacovigilance

Boost the productivity of Contraindication Discovery• Scientists process a higher number of more relevant sources in less time

and develop faster and deeper insight into the specific context.• Discover and Investigate unexpected ADRs faster• Discard ADRs that are expected• Develop Contraindication insights faster



Boost the productivity of Contraindication Discovery Minimize social costs associated with adverse events

• Avoid un-necessary exposure of sensitive populations to the drug• Modify Drug Labelling faster• Remove toxic products from the market earlier



Boost the productivity of Contraindication Discovery Minimize social costs associated with adverse events Minimize corporate risk associated with ADRs

• Reduced public exposure means reduced number of legal proceedings



Boost the productivity of Contraindication Discovery Minimize social costs associated with adverse events Minimize corporate risk associated with ADRs Open new areas for growth

• Reuse ADR knowledge in future Research• Some unexpected side effects can be considered therapeutic effects elsewhere• Discover alternative uses for a given drug


Unique benefits of TEMIS offering in Life Sciences

Long experience with the Pharma industry and specialized in-house expertise




Specialized components for Scientific Discovery and unique technical differentiator : Relationships detection• The powerful semantic models embedded in our off-the shelf components

(Biological, Chemical and Medical SkillCartridges ) detect entities such as disorders, targets, leads, and side-effects, as expressed in scientific litterature, AS WELL AS the relationships that bind them.• You don’t need to invest any time or effort in developping semantic expertise to

benefit from advanced extraction capabilities. We do that for you.




Specialized components for Scientific Discovery and unique technical differentiator : Relationships detection

Fully customizable Platform• Standard SkillCartridges can be further customized and bespoke SkillCartridges can

be developped to adjust specifically to your therapeutic areas of focus or R&D strategies. We provide the tools, training and services required to expand the out-of-the-box capabilities of the platform and customize them to your own way of working.




Specialized components for Scientific Discovery and unique technical differentiator : Relationships detection

Fully customizable Platform

Low TCO thanks to Enterprise Platform approach• Luxid provides Text Mining benefits across the entire organization, not only to

departments focused on Scientific Discovery. Our capabilities include Competitive Intelligence, Sentiment Analysis and Pharmacovigilance. This creates opportunities for economies of scale in several areas, including administration and training. We can even reduce administration costs further by hosting the platform for you.

Thank you – Q& A

Daniel Mayer, Product Marketing Manager [email protected]

Olivier Feller, Life Sciences Consultant [email protected]

Pharmacovigilance the OTHER discovery process in Pharma Daniel Mayer, Product Marketing Manager...

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