1. Progress Report on the Patient Reported Outcomes Harmonization Team
Jean Paul Gagnon, PhD
Aventis Pharmaceuticals Inc.

2. Objectives Discuss Historical Development Describe Forum Outcomes
Outline Future Activities

3. Objectives
Discuss Historical Developments

4. Who started the PRO Harmonization Group?
European Regulatory Issues on Quality-of-Life Assessment (ERIQA)
International Society of Pharmacoeconomic and Outcomes Research (ISPOR)
International Society of Quality of Life (ISOQOL)
Pharmaceutical Research and Manufacturers of America (PhRMA) Health Outcomes Committee (HOC)

5. What is its mission? To harmonize Patient Reported Outcome
issues used in drug development and
Evaluation.

6. What are its objectives?
Clarify areas of concern or confusion about PRO evaluation
Explain the added value of PRO outcomes among all key players, i.e., academics, regulators, industry researchers, prescribers and patients
Open and maintain communication between key players
Disseminate meeting outcomes, i.e., to publish papers, to participate in conferences

7. Objectives
Discuss Historical Development
Describe Forum Outcomes

8. Forums Three Harmonization Forums held March 31, 2000 Sept. 14, 2000
February 16, 2001
Representatives from ERIQA, ISOQOL, ISPOR, PhRMA HOC and FDA observers

9. March 2000 Meeting Objectives
Discuss problematic issues
Harmonize recommendations proposed by each organization
Recommend solutions when none exist
Proposed future steps to achieve consensus on problematic issues

10. Meeting Outcomes
Consensus and areas of disagreement were identified in four areas: Concept, Study Design, Interpretation and Conditions for Claims*
Group agreed to continue discussion and form a coordination group with representatives from the four organizations to organize future meeting
Real issue “does outcomes research provide added value”
*Report available on-line:

11. Impact of Outcomes Data
Can the added-value of the outcome be demonstrated, i.e., what does the outcome provide beyond traditional measures?
Does the subjective impact of treatment provide value over observer-based assessments or simple symptom scales?
Does the measure capture information that is missed with traditional measures?

12. September 2000 Meeting Outcomes
Conceptual framework was broadened to Patient Based Assessment (PBA) which was changed to Patient Reported Outcomes (PRO) for clarity
Decision made to continue discussions and schedule meeting with FDA and EMEA representatives

13. February 2001 Meeting Objectives
Clarify aspects and components of PRO evaluation
Discuss where PRO can add value to clinical endpoints
Suggest use of this information within labeling and promotional claims

14. Take Away Points
Patient has a unique voice and valuable perspective that should play a role in medical decision making
PROs can be measured in reliable and valid ways
PROs are increasingly used as efficacy endpoints in randomized controlled trials

15. Patient Outcomes Assessment Sources and Examples
Clinician - Reported
Patient - Reported
Physiological
Caregiver - Reported
For example,
Global impressions
Observation & tests
of function
For example,
FEV1
HbA1c
Tumor size
For example,
Dependency
Functional status
Global Impression
Functional status
Well-being
Symptoms
HRQL
Satisfaction with TX
Treatment adherence
Assessment of outcome can be achieved in several ways, but most robust involves repeated application of a standardized measurement. Outcome can be defined as a change in this measurement parameter
Locates outcome parameters within their primary setting. e.g. clinical or biological markers as tumor size are primarily located within the professional domain. However, parameters such as B/P may be measured by others (e.g. patients).
Productivity not included as it is secondary to function

16. Areas of Agreement
Patient Reported Outcomes (PRO) evaluation is a valid concept
PRO can be operationalized
PRO claims should conform with the evidence and be pre-specified
PRO should be reported with fair balance in labeling and promotional claims

17. “Objective” “Subjective”
This cartoon concludes what HRQOL stands for..
It is actually not the objective exercise test data in an hospital environment that we measure but the everyday activities at home or at work subjectively perceived by the patient himself
Efficacy is often difficult to measure in disorders for which the patients subjective experience of symptoms and therapy and their impact is critical.
“Objective”
“Subjective”
Exercise test versus physical functioning, r = 0.40
Wiklund I et al.
Clin Cardiol 1991;14

18. Objectives Discuss Historical Development Describe Forum Outcomes
Outline Future Activities

19. Future Plans for Pro Team
Publish article on work to date, draft manuscript prepared
Develop slide presentations for conferences, e.g., ISPOR, ISOQOL, DIA, others
Supply content via website
Continue to hold forums until deemed unnecessary
Measure outcomes from Forums

20. February 2002 Forum Agenda
Instrument development: what are the standards
Instrument selection: demonstrating hypothesis, relationships to measurement
Statistical issues: focus on handling missing data
Interpretation: Interpreting changes that are not consistent between outcomes

21. Summary Discussed Historical Developments Described Meeting Outcomes
Outlined Future Activities

22. QUESTIONS Jean Paul Gagnon jean. gagnon@aventis
QUESTIONS Jean Paul Gagnon Aventis Pharmaceuticals Inc.