eSource: Changing the Monitor / Site / Sponsor Relationship

Edward S. SeguineCEOClinical Ink

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Discussion Points

• What is eSource?

• Industry Metrics

• Business Model Implications

Audience Participation REQUIRED

Vote via Texting

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Poll: My primary work role is:

Practice Poll

What is eSource?

IVRS / IWRS

Digital Equipment (BP Cuff, EKG)

ePRO

Imaging Data EMRs ??

Electronic Source Documentation “This guidance is intended to promote the capture of source data in electronic form, which will help to:

– eliminate unnecessary duplication of data,

– reduce transcription errors,

– promote real-time entry of electronic source during subject visits,

– ensure accurate/complete data through electronic prompts”

FDA “We’re Here To Help”

FDA Perspective“For the purpose of this guidance, the terms eSource

documents and eSource data are used to describe source documents and source data for which the original record and certified copies are initially captured electronically.” (page 6)

“The eCRF is a vehicle used to assemble all the data from different electronic- and paper-based systems and makes it possible to capture and organize these diverse data in a manner that satisfies the study protocol and that enables the data to be systematically reviewed and analyzed.” (page 6)

Risk-Based Monitoring

“The guidance specifically encourages greater use of centralized monitoring methods where appropriate… The extent to which centralized monitoring practices can be employed will depend to some extent on accessibility of electronic records.” (page 1, 8)

“Source data verification and other activities traditionally performed by on-site monitoring can now often be accomplished remotely.” (page 5)

FDA “We’re Here To Help”

Poll: How much was spent on Phase 1-3 Clinical...

Poll #1

Poll #1

How much was spent on Phase 1-3 clinical trials last year?

$40 BILLION$1,200,000 for EVERY employee

involved in clinical trials

Source: Medidata CRO Contractor Fact Sheet; June 2012

Total Clinical Trial Costs

29%

26%

18%

12%

6%5% 4%

Monitoring Spend

R&D Spend Monitoring

Phase 1 $5.6B $1.2B

Phase 2 $8.8B $2.7B

Phase 3 $25.4B $7.9B

TOTAL $39.8B $11.8BSource: 2012 PhRMA Industry Report

UNSUSTAINABLE!

Clinical Trials Today

# Days Task Category

0 Record patient data on paper forms SOURCE

2 – 10+ Manually input data into database EDC

30 – 60+ On-site comparison of Source to EDC MONITOR

Clinical Trials Tomorrow

# Days Task Benefit

0 Record patient data on electronic forms No Paper

0 Automatically record to database No Errors

0 Remotely review source docs via web No Travel

Poll: Direct entry into CRFs meets site GCP re...

Poll #2

Source ≠ CRF

Criteria Source CRF

Timing Original Secondary

Workflow Site/Subject Sponsor

DataGCP/Protocol;Unstructured

Analysis; Structured

Owner Investigator Sponsor

Validation Review Verify

Explicit FDA requirements for Source21 CFR 312.62(b) Patient Case History

Source ≠ CRF: PE - eCRF

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CDASH Preferred Option A (5.14.1)

Source ≠ CRF: PE – Paper Source

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Source ≠ CRF: PE – eSource

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CRF ≠ Source: Vitals - eCRF

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CRF ≠ Source: Vitals – Paper Source

CRF ≠ Source: Vitals – eSource

Poll: Reviewing CRFs remotely is sufficient to...

Poll #3

Site Responsibility for Source

Inadequate/inaccurate case history is 2ND most common site audit finding

“Failure to maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation” - cited in 60% of investigator warning letters

“What is not documented is not done”

ICH E6 separates source DOCUMENTS from source DATA

Impact on Monitoring PlanSource Data Verification: what data does

need to be verified for accuracy

Source Document Review: what documents should be reviewed for context, trends, etc.

Remote Monitoring: what types of trial data, how frequently, with what tools

Changing Source data: where will changes be made, by whom, when, where is audit trail

Monitor – Site Communication

Fewer onsite visits, but more frequent and relevant site interactions

Data clarified by viewing context of document

Queries - total number and response time are reduced

Centralized tools ‘track’ monitor activity; what % of documents reviewed, how long?

Practical Realities

At what level is data signed? Investigator “signs” CRF, do they need to “sign” eSource

eSource design intent versus database; difference between “Yes”, “No”, “Null” values

Eliminate duplicate edit checks; if checked at source, no need for second check

Not all site employees have email address; how to verify identity, grant access

Drawbacks of Targeted SDV

Reliance on EDC data - not Source

No source document review

No benefit to site workflow

Sponsor discretion and risk

Sounds new; but really old

Reliance on process, not technology

Contact Details

Ed Seguine

CEO – Clinical Ink

336-464-0702

eseguine@clinicalink.com

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