DFUG 2007 March 11 - 14, 2007

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The Case Study Toolfor Study Validation and Training

Prieya Wason, Dylan Nguyen, & Valerie L. WarburtonPDL BioPharma, Inc.

PWason@pdl.comDNguyen@pdl.comVWarburton@pdl.com

The Case Study (CS) tool

Conceived as a vehicle for deliveringstructured Datafax and CRF training

to clinical sites via CRO monitors.

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Challenge: Deliver Consistent Training

Larger-scale trials associated withincreasing layers of separationbetween the DataFax expert and theindividual responsible for reporting data.

Components

• “Subject” Narrative

• Visit Scheduler

• Annotated CRFs in CS Subject Binder

• Images in DataFax

• Faxlog for each visit

• QC Reports

Four stages of development…

DFUG 2007 March 11 - 14, 2007

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I. Preparation

Construct Visit SchedulerCRF v2

Identify Data Sources– Prior/template studies

• Generic data• Indication-specific

– Data Consultant (CSDC)

2nd Draftprotocol &Start ofCRF Dev.

ProcessTrigger

• Indication-specific data Prior study

Identify data source(s)

I. Preparation

Consultant expert– Site Coordinator

(CSDC)– Study CRO– Medical Monitor

(fill in the remainingblanks!)

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I. Preparation

• Constructed from the Schedule of Assessments

Visit Scheduler

01-Apr-06

I. Preparation

• Generates expected visit dates (based on date of Day 0)

Visit Scheduler

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Visit Scheduler provides:• Underlying structure for the CS and narrative• Reference outline for database setup

Deviations

04-May-06

MISSed Visit

I. Preparation

II. Construction

Study Initiation MeetingeCS

• Check against requirements list• Write Sample Patient Narrative

CS Hardcopy

Electronic construction (eCS)“Q.A.”edCRFs

Bundle Scheduler, Narrative, & CS hardcopy for review

CS Draft

Hand-completion of CRFs by CRA/CSDCCRF v3

ProcessTrigger

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II. Construction

• Sample of corrections made to a CRF(line thru, initial, date, new value)

• Log forms – added information (initial,date)

• CRFs completed in error

• Manual page numbering

• Unknown and partial dates

• Other study-specific elements

• Interim Visits (if applicable)

Elements of Case Study data

• Missing header information

• Out of range sample data

• Inconsistent data

• Nonsensical data

• Missing values

Items to Trigger Data Queries:

II. Construction

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• Provides conceptual structure for CS Binder• "Script" for CRO training of sites

Create the Narrative from CS hard copy

II. Construction

• Easy for TDS to replace underlying master pages withFinal CRFs.

• Electronic overlay of data removes the need to repeathand-completion.

Electronic version of CS

II. Construction

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• CRFs designed in Framemaker

• eCS created using InDesign (CS2!)

• InDesign allows layer-level locking & show/hide:– Header (Master)

– CRF (import PDF)

– Initial completion

– Correction &Initial/Date

– Extra layers forlog CRFs

II. Construction

Electronic version of CS

III. Validation

Initial faxing, data entry, QCseCS

Review– corrections as necessary

ValidatedeCS

• Electronic version of faxlogs• CRFs corrected & refaxed

QC report

ProcessTrigger

DFUG 2007 March 11 - 14, 2007

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Initial faxing and data entry

• Tests study setup with realistic data

• Trains CDA on data entry

• CDC provides feedback on edit checks

III. Validation

• Provides conceptual structure for CS Binder• "Script" for CRO training of sites

Creation of QCs and QC Reports

III. Validation

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• Data correction and QC resolution

• Results in full, sequential electronic CS(primary and secondary images)

“Re”faxing of corrections

III. Validation

IV. Approval, Production, & Rollout

DistributionPrint CS

• Select CS examples for integration with CRF Completion Guidelines• Print CS Training binders

Final CRFs

Formal Sign-off ProcessReviewedCS

• Train the trainer• Train end-users (Site Initiation Visit)• Ongoing training

Training

ProcessTrigger

DFUG 2007 March 11 - 14, 2007

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• Select subset for inclusion in Guidelines

– At least one example of each unique CRF

• Concise tool for site trainingand support.

• Reference material for sites

CRF Completion Guidelines

IV. Approval and Production

Training modules

• Framework (Narrative, Scheduler)

• Multiple Scenarios

• Contextual examples

• Sample QC reports specific to study

• CRF Completion Guidelines (illustrations)

DFUG 2007 March 11 - 14, 2007

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Lessons

CS tool has matured through use in six studies to date.

CON:• Developed “at risk”

• Increases time to database readiness

PRO:• Independent review of CRFs and study flow by

subject-matter expert

• Role in validating and testing the database

Expanded role in Validation

• Study flow

• Design and printing of CRFs

• CRF Completion Guidelines

• A secondary check of database setup

DFUG 2007 March 11 - 14, 2007

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Standardized Training

The role of the CS in training has expanded to targetthe following:

Data field particulars and editchecks

Data ManagementStaff

Monitoring review of study andDataFax-specific issues

CRAs

General DataFax review;CRF Completion Review

Clinical site staff

Study FlowAll users

IV. Approval & Production

I. Preparation

II. Construction

III. Validation

Four phases