Information support for decision making. Christopher Hart 2012

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

Christopher Hart | 10 October 20122 Research & Development | Biometrics & Information Science

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

3 Christopher Hart | 10 October 2012 Research & Development | Biometrics & Information Science

Clinical development as an iterative cycle

Design

Execute

Interpret

Decide

Design decisions


ConstraintsScrutiny of R&D can increase quality


http://availagility.co.uk/wp-content/uploads/2009/12/Triangle.png

- 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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4

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

Christopher Hart | 10 October 2012

7Research & Development | Biometrics & Information Science

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.

…

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



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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4



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



Preliminary DesignClinical support for early projects


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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Research & Development | Biometrics & Information Science

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

http://astrazeneca.citeline.com/account_alert.asp?intSharedSearchID=&tID=&qID=&target=

https://www.pharmapendium.com/home.do

Creating Program OptionsCompetitive review


Creating Program OptionsCompetitive review


Creating Program OptionsDevelopment strategies


Creating Program OptionsDevelopment strategies


Creating Program OptionsDefining reasonable duration


Creating Program OptionsDefining reasonable duration


Creating Program OptionsComparative safety review


Creating Program OptionsComparative safety review



Design

Execute

Interpret

Decide

Decision making during the study


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


An Efficient Clinical Trial


Design

Execute

Interpret

Safety oversight

A More Efficient Clinical Trial?Ongoing review


Design

Execute

Interpret

Review Prepare

Ongoing Review

Operational

• Data entry lag

• Set up• Cost• Resource

Systemic

• Standards• Technology• Training• Familiarity

Obstacles


Ongoing Review

• “Statistically guided review of clinical data”• Colloquially called ‘Data Review Tool’

- S-Plus based

Creating a consistent foundation


Guided Data ReviewExample lab data


Guided Data ReviewShift plots


Guided Data ReviewAdverse event incidence


Guided Data ReviewGroup comparison plot


Guided Data ReviewLooking at a patient’s data


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


Ongoing ReviewExample population lab data


Ongoing ReviewExample population lab data


Ongoing Review

• data review tools- real time- statistically guided- interactive- intelligible

An essential activity in drug development



Design

Execute

Interpret

Decide


Set up

Execute

Analyze

Set up

Execute

Analyze

Accurate Forecasting Affects AnalysisSometimes things take longer than planned


Set up

Execute

Analyze

Decide

Less is MoreFewer static reports help interpretation


Traditional Trial ReportingA phase 2 study, 210 patients


Presenting Our ResultsContemporary technology


Setting the Rules for a Decision

Design

Execute

Interpret

Decide

Design with the end in mind


Great Design Should Give Good ResultsEasy, unambiguous interpretation of results


Shades of EvidenceEasy, ambiguous interpretation of results


Complex Measures Expert interpretation is needed


pre post

Openness and Simplicity Help

• Clear criteria

• Explicit assumptions

• Predefined analyses

• Immediate access to interpretable trial data


Setting the Rules for a Decision

Design

Execute

Interpret

Decide

Anticipating changes


To the FutureExperts with information at their fingertips


Clinical applications project


To the Future


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


Linked Data Are Changing What We Can DoLinked open data in 2011


Linking Open Data cloud diagram, by Richard Cyganiak and Anja Jentzsch. http://lod-cloud.net/

Increasing Interest in Linked DataAn evolving set of tools


Open Data Let People Do MoreYou can apply your own perspective


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


[myhealthevet] provides you opportunities and tools to make informed decisions

http://www.patientslikeme.com/

http://www.patientslikeme.com/

http://www.microsoft.com/en-gb/healthvault/default.aspx


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


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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Information support for decision making. Christopher Hart 2012