Tools, Glossary & Appendix Provided for Dossier Submission

The PRO Final Guidance announced last e

December helps Sponsors and CROs

understand how to include the patient

viewpoint in the clinical trials that support

market authorization for their medical

products. The Guidance shows that FDA

understands the pivotal role of PRO measures

in establishing clinical benefit.

Final FDA Guidance Brings PRO and ePRO Mainstream

Contents

Key Takeaways from FDA Final Guidance on PRO

2

Diagram of the Conceptual Framework of a PRO Instrument

2

Recommended Key Strategies for Sponsors

3

Appendix may be used as a Dossier Outline 3

Other Links on Current Industry PRO Developments

4

This Insights edition is

dedicated to ePRO

mentioned within the

Final Guidance, and

intended to provide readers

with an executive summary

of the new document with

respect to ePRO.

Key Takeaways from FDA Final Guidance on PRO

As a result of this collaborative instructional document, ePRO use within clinical trials will significantly grow,

as more therapies that include the patient perspective are developed by industry.

Figure 4. Diagram of the Conceptual Framework of a PRO Instrument

Figure 3. Development of a PRO Instrument: An Iterative Process

Section lll of the Final Guidance

i. Hypothesize Conceptual Frameworktl hypothesized potentte in onte in n/ riyp or st tion)

or lite re/exper reviework

in endpoint lnt in deve ent

PRO↕

Claim

v. Modify Instrument,

ii Adjust Conceptual Framework and DraftInstrument

s

iii. Confirm Conceptual Framework and Assess Other Measurement Properties

s

iv. Collect, Analyze, and Interpret Data

)

Item 1

Item 2

Item 3

Item 4

Item 5

Item 6

Domain 1

General Concept

Domain 2

Final FDA Guidance Brings PRO and ePRO Mainstream

2

1

3

4

2

Sponsors should avoid the following:Direct PRO data transmission from the ePRO data collection 1.device to the sponsor, clinical investigator, or other third party without an electronic audit trail.

Exclusive e-source document control by the sponsor.2.

Inability of the clinical investigator to maintain and confirm3.electronic PRO data accuracy.

The existence of only one database without backup.4.

Ability of any entity other than the investigator (and/or site 5.staff designated by the investigator) to modify the source data.

Loss of adverse event data.6.

Premature or unplanned access to unblinded data.7.

Inability of an FDA investigator to inspect, verify, and copy 8.the data at the clinical site during an inspection.

An insecure system where records are easily altered.9.

Direct PRO data transmission of important safety information10.to sponsors, clinical research organizations, and/or third parties,without ensuring the timely transmission of the data to theclinical investigator responsible for the patients.1

Please note that numbers 3 and 10 were not present in the Draft, and they both insist on the role of the Clinical Investigator preparing and maintaining the patient data to meet the intention of the Final Guidance.1This concept was not mentioned in the FDA Draft Guidance

Recommended key strategies for Sponsors, based on the Final Guidance:

Plan an endpoint model that shows the relationship 1.between your planned claims and the measures, including the PRO measures.

Choose instruments for PRO that are capable of measuring 2.what you want to know for your claim.

Establish content validity first, then other measurement 3.properties.

Take advantage that PRO can be migrated to e-versions. Verify 4.measurement properties based on the amount of change.

If questionnaire completion is unsupervised, explain how5.you know the diaries were completed at specified times.

Begin the selection and development of your PRO measures6.early, since this must be done by time of confirmatory trials.

Include final versions of the questionnaires (on paper or 7.electronic if appropriate) in protocols.

Prepare PRO dossier using the Guideline’s Appendix.8.

3

Final FDA Guidance Brings PRO and ePRO Mainstream

LogPad®

SitePad®

StudyWorks®

eSense™ Sensors

ePRO Designer

Study Archive

PROVision™ Scientific Services

Trial Success Program™ (TSP)

PHT System Support Center

Scientific Review and Validation

Site Telecom Assessments

Technology Transfer

PHT LogPad – The mobile dHand Held for home eDiaries

PHT Electronic Patient Reported Outcome(ePRO) System Components

4

The FDA Final Guidance: Key Considerations for Sponsors Collecting PRO and ePRO Data

PHT Corporation Comments on New FDA Guidance for Industry.

The Pros of ePRO,

PHT Corporation

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Boston, MA 02129 USA

Toll-Free: 877.360.2901

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2, chemin Louis-Hubert

1213 Petit-Lancy, Geneva, Switzerland

Phone: 41.22.879.91.00

Insights Q1 2010

www.phtcorp.com

Copyright © 2010 PHT Corporation

Rev 3.10

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