information support for decision making. christopher hart 2012
TRANSCRIPT
Decisions, Decisions, Decisions
Oncology Clinical Development Congress 10 October 2012Christopher HartClinical Information Management Director, Oncology Clinical Discovery Team
Information support for decision making
The Current Climate
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Iconograph by Reid Parham
Making a Meaningful Difference to PatientsSupporting experts in making decisions
•Focusing the efforts of our experts•Effective use of the most relevant information
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Clinical development as an iterative cycle
Design
Execute
Interpret
Decide
Design decisions
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ConstraintsScrutiny of R&D can increase quality
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- Create program optionsfrom study prototypes
- Assess program optionsfrom an operational and a likelihood of success point of view
Creative Process for Program Design
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DELIVERPROGRAM
OPTIONS FOROPTIMAL COST,
SPEED &CERTAINTY
Identifyquestions
Identifypotentialmeasures
Createstudy
prototypes
Createprogramoptions
- Identify what key questionsneed to be answered for thenext Investment Decision
- Identify the potential measuresthat could be used to answereach clinical question
- Use integrative thinking to come up with different studyoptions that could deliver each measure (i.e., consider study population, treatment, locations, etc)6 Christopher Hart | 10 October 2012 Research & Development | Biometrics & Information Science
Workbench - Key Benefits
CREATIVITY TRANSPARENCY CUSTOMERINTIMACY
STANDARDISATION
CollaborationExperts assigned to address key uncertainties
Knowledge re-useLeveraging knowledge from past and parallel projects
Integrative thinkingSuperior options synthesized through multi level design process
Transparent DecisionsDecisions based on robust, documented evaluation of options, are tied directly to desired business outcomes
Track changes and understand impactChanges are visualized and traced, with impact on related decisions marked to ensure consistency
Project TeamsA well defined design process, along with best practice, allows designers to focus on making expert decisions
GovernanceAccess to full thinking and rationalization behind proposals
Early input of expertsAbility to capture input of experts flexibly, at an early stage
Recyclable processEnsure that best practice continues to be evolved, and uniformly used
Recyclable knowledgeDesign thinking becomes accessible design knowledge
Standards from the StartStandardized design will lead to standard data capture, reporting, and data utilization
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Building a “Workbench” for Clinical Trial Design
Clinical Claims: How likely are we to succeed? Where do we need to be at next investment decision?
Efficacy Claim Safety Claim
Benefit Questions Risk Questions
Major measure options Minor measure options
Options for Design elements
Assessment Comparator Design Location PopulationTreatment
Benefit/Risk/Value Clinical questions are created, stated in a measurable way, aimed for next investment decision.
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Study prototype options
Program options
Optimal CostOptimal RobustnessOptimal Speed
Clinical studies
Each Clinical question is broken down into potential Major and Minor measures, which are assessed.
Measures are further worked up through assessing options for Design elements.
Prototype studies are pulled together from Design elements. Statistical and operational information is worked up, e.g. Sample size, Duration, Power, Cost, TimePrototype studies are pulled together to form a program option optimized for Cost, Speed and Robustness. Statistical and operational information is finalized.
Value Claim
Value Questions
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Des
ign
rem
itD
esig
n Pr
ogra
m o
ptio
ns
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Measures and Design elements
Identify Potential measuresEach Clinical question is broken down into potential Major and Minor measures, which are assessed.
Create options for Design elementsA Major measure is further worked up through assessing options for Design elements. Possible Minor measures are pulled in from the same or other Clinical questions
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Study prototypes and Program options
Create Study prototypes Prototype studies are pulled together through combining Design element options.
Statistical and operational information is worked up, e.g. Sample size, Duration, Power, Cost, Time.
Create Program optionsPrototype studies are pulled together to form a program option optimized for Cost, Speed and Robustness.
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Refining and Evaluating Options
RefineAt the very end of the process, the design team pulls together the appropriate options to compose Program options for Cost, Speed and Robustness.
EvaluateAfter combining options, Workbench helps the team evaluate the options. The team defines important “Success factors”, e.g. for Location “Regions are preferred from a Patient prevalence perspective”.
This captures the strategic thinking of the team and helps them use creativity to identify superior options
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Preliminary DesignClinical support for early projects
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Clinical MeMostudies
Human tissue target linkage
Conduct Method & Model studies
needed to qualify Proof of Mechanism
and Proof of Principle
biomarkers for use in early clinical
studies
Provision of human tissue for target linkage throughout the discovery / development cycle
Discovery access to a
clinical voice
An early accessible & consolidated
clinical voice into the developability of target and drug
Information SupportExperts supporting experts
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Chemistry and Patents Current Awareness
News Company Profile and Pipeline Information
Competitive Intelligence Literature and Clinical Trials
Literature and
Chemistry/ Patent Alerts
Key Opinion Leaders and Associations
LiteratureLinked to Full-text articles
Alert SystemAligned to Target
Portfolio
Expertise in Tools and ResourcesPatent Analysis
Patent Analysis with STN Anavist
Chemistry Structure and Reaction
Searches
IP Research Landscape
Prior Art Searches- Before patent filings
- New target evaluation
- For alternative indications,
collaborations, etc.
Mapping potential
opportunities
Clinical Trials
Creating Program OptionsCompetitive review
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Creating Program OptionsCompetitive review
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Creating Program OptionsDevelopment strategies
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Creating Program OptionsDevelopment strategies
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Creating Program OptionsDefining reasonable duration
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Creating Program OptionsDefining reasonable duration
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Creating Program OptionsComparative safety review
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Creating Program OptionsComparative safety review
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Clinical development as an iterative cycle
Design
Execute
Interpret
Decide
Decision making during the study
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Prompt Data Review
• 21CFR312.32 IND safety reporting- “(b)Review of safety information . The sponsor must
promptly review all information relevant to the safety of the drug … including information derived from any clinical … investigations…
• ICH E6R1- 4.11.2 Adverse events and/or laboratory abnormalities
identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol.
A requirement
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An Efficient Clinical Trial
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Design
Execute
Interpret
Safety oversight
A More Efficient Clinical Trial?Ongoing review
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Design
Execute
Interpret
Review Prepare
Ongoing Review
Operational
• Data entry lag
• Set up• Cost• Resource
Systemic
• Standards• Technology• Training• Familiarity
Obstacles
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Ongoing Review
• “Statistically guided review of clinical data”• Colloquially called ‘Data Review Tool’
- S-Plus based
Creating a consistent foundation
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Guided Data ReviewExample lab data
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Guided Data ReviewShift plots
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Guided Data ReviewAdverse event incidence
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Guided Data ReviewGroup comparison plot
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Guided Data ReviewLooking at a patient’s data
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Ongoing Review
• REACT: REal-time Analytics for Clinical Trials
• We use it for the early assessment and ongoing monitoring of adverse events during a clinical trial.
Putting more in the hands of the expert
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Ongoing ReviewExample population lab data
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Ongoing ReviewExample population lab data
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Ongoing Review
• data review tools- real time- statistically guided- interactive- intelligible
An essential activity in drug development
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Clinical development as an iterative cycle
Design
Execute
Interpret
Decide
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Set up
Execute
Analyze
Set up
Execute
Analyze
Accurate Forecasting Affects AnalysisSometimes things take longer than planned
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Set up
Execute
Analyze
Decide
Less is MoreFewer static reports help interpretation
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Traditional Trial ReportingA phase 2 study, 210 patients
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Presenting Our ResultsContemporary technology
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Setting the Rules for a Decision
Design
Execute
Interpret
Decide
Design with the end in mind
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Great Design Should Give Good ResultsEasy, unambiguous interpretation of results
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Shades of EvidenceEasy, ambiguous interpretation of results
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Complex Measures Expert interpretation is needed
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pre post
Openness and Simplicity Help
• Clear criteria
• Explicit assumptions
• Predefined analyses
• Immediate access to interpretable trial data
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Setting the Rules for a Decision
Design
Execute
Interpret
Decide
Anticipating changes
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To the FutureExperts with information at their fingertips
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Clinical applications project
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To the Future
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Increasing Transparency
• NEJM editorial on the USA Trial and Experimental Studies Transparency Act
• “…clinical trials should be conducted in the open, with full public knowledge of the question asked, the intervention tested, and the results obtained. The TEST Act is another step toward this end, and we strongly support it.”
• European Medicines Agency statement - “…it will proactively publish clinical trial data and enable
access to full data sets by interested parties.”
• EFPIA statement- “EFPIA, the voice of the research-based pharmaceutical
industry, welcomes all moves to remove perceived secrecy, as long as legitimate trade secrets are protected”
The call and the response
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Linked Data Are Changing What We Can DoLinked open data in 2011
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Linking Open Data cloud diagram, by Richard Cyganiak and Anja Jentzsch. http://lod-cloud.net/
Increasing Interest in Linked DataAn evolving set of tools
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Open Data Let People Do MoreYou can apply your own perspective
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Health DataAccessible? Open?
• Because of PatientsLikeMe, we are better able to recognize warning signs... [and] keep things in perspective. In short, PatientsLikeMe empowers us.
• PatientsLikeMe has provided me with new friends- people who are experiencing the same problems as I am.
• I joined because I didn't want to feel alone anymore. Simply put. And I knew that I could be helpful [by sharing] my experience.
• www.patientslikeme.com
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[myhealthevet] provides you opportunities and tools to make informed decisions
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In summary
• Make better use of experts’ time by focusing effort- Make best use of available information in ways experts can
use- Keep things simple- Embrace the available technologies and cultural changes to
make the most meaningful difference for patients
Make the biggest difference possible
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Acknowledgements
• AstraZeneca- Andrew Hughes, Anita Lindsay, Louise Grochow, Laszlo
Vasko, Nina Mian, Amrik Mahal,Jjames Weatherall, Harry Southworth & Dónal Landers
• Thomson Reuters- Tim Miller, John Cole & Richard Chamier
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