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10/26/11

An early look at 

Confirm Success with East®  Clinical Trial Design Software System 

on the Architect™ platform 

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1 Europe East UGM2011

•  East today •  Software vision •  Example in hypertension •  East® demo •  Design questions

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agenda 

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47oftheTop50biopharmaceu4calcompaniesuseCytelso:ware!+alldivisionsoftheFDA

an industry standard 

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what East has changed 

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Software vision 

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•  Can I create designs in batches? •  How should I choose the timing of the interim analysis? •  How would I specify a first interim analysis strictly for futility

followed by a second interim analysis for both efficacy and futility?

•  Can I customize the information I would like to use in a report?

•  Can I specify my futility boundary in terms of conditional power or effect size?

•  What are the true savings in sample size if you consider accrual patterns and overruns?

•  Given observed data at an interim, can I compute the probability of success or simulate the rest of the trial?

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Design questions 

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•  Phase 3 clinical trial testing superiority of an angiotensin II receptor blocker vs. placebo

•  Primary endpoint: change from baseline to week 6 in the 24-hour mean systolic blood pressure by ambulatory blood pressure monitoring

•  Test the difference of two independent means using a 1-sided a = 0.025

•  Would like the trial to have 90% power to detect an effect size of δ = -1.5 mm Hg when compared to placebo in a 1:1 allocation

•  Can assume a common standard deviation of σ = 6 mm Hg •  Accrual rate of 40 patients per month

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Example in hypertension 

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East® Demo 

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•  Ease of use •  Reliability •  Productivity •  Communication •  Advanced functionality using R •  Breadth of designs available •  Powerful simulation capabilities

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benefits of East 

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Peace of Mind with ACES® Controlled and Secured Trial Execution System

Business Confidential 26 October 2011 11

•  Are interim decision rules pre-specified? •  Are they carried out as pre-specified? •  Who has access to them? •  Who prepares the interim report? •  Who has access to the interim report and how is

confidentiality maintained? •  Can interim results be reverse engineered from

actions taken?

logistical and operational biases 

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no problem 

“A well-trusted firewall established for trial conduct beyond those established for conventional group sequential trials can help provide assurance that statistical and operational biases have not been introduced.”

FDA Guidance on Adaptive Design (2010)

what is required? 

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•  Web based technology to control flow of information and access to confidential documents

•  Prevents operational bias by including the actual adaptive algorithm only in restricted appendix to Data Monitoring Committee (DMC) charter and tracking access to this document

•  Establishes trustworthiness through secure password protected access to documents, execution of algorithms, and audit trail

ACES: Access Control Execution System 

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Create Documents (Protocol, SAP, DMC Charter)

Store/Archive Documents

Enroll Subjects &

Collect Responses

Send Response

Data to ISC

Perform Analysis and

Create Reports

Send Analysis to

DMC

Spo

nsor

IS

C

DM

C

Make Recommendati

on

Send Recommendation to Sponsor/

Steering Committee

Make Decision

about Trial

Ste

erin

g C

omm

ittee

After decision… 1. DMC notified 2. Drug Supply notified 3. IVRS notified

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traditional process 

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•  Inconsistency •  Insecurity •  Process Enforcement •  Firewall Enforcement •  Lack of Audit Trails

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Concerns with Traditional Interim Analysis Processes

why do we need ACES? 

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Create Documents (Protocol, SAP, DMC Charter)

Store/Archive Documents

Enroll Subjects &

Collect Responses

Send Response

Data to ISC

Perform Analysis and

Create Reports

Send Analysis to

DMC

Spo

nsor

IS

C

DM

C

Make Recommendati

on

Send Recommendation to Sponsor/

Steering Committee

Make Decision

about Trial

Ste

erin

g C

omm

ittee

in ACES

in ACES

in ACES

After decision… 1. DMC notified 2. Drug Supply notified 3. IVRS notified

in ACES

ACES process 

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• Automate Analyses •  Improve Efficiency • Reduce Bias • SAS Integration • R Integration (planned)

Workflow Automation

• Centralized Access • User Security • Audited Access • Categorization

Document Storage

• Protect Data and Information

• Maintain Blind • Protect Study Integrity • Reduce Bias

Secure Firewalls

• 21 CFR Part 11 Compliant

• System and Study Level Reporting

• All Access Recorded • Guarantees “Who Saw

What and When”

Auditing

• Make Better Decisions • Make Earlier Decisions • SAS Integration • R Integration (planned) • Customizable

Reporting

• Supports All Major Browsers

• SaaS Hosted Solution • 128-bit SSL Encryption

Global Access

how can ACES help? 

Thank you Questions about East®? Call +1.617.661.2011 http://www.cytel.com/software/east.aspx

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Q&A 

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