ISPOR Participates in Efforts to Harmonize Regulatory Requirements for Patient Reported Outcomes

by Nancy Kline Leidy PhD, RN, MEDTAP International, MD, USA

ISPOR is one of four organizations participating in discussions with pharmaceutical regulatory authorities about the use of health-related quality of life (HRQL) and, more recently, patient reported outcomes in pharmaceutical research and communication, specifically labeling and promotion. Representatives of the ISPOR, the International Society for Quality of Life Research (ISOQOL), the European Regulatory Issues on Quality of Life Assessment (ERIQA) group, and the Pharmaceutical Research and Manufacturers of America Health Outcomes Committee (PhRMA-HOC) have met with representatives of the United States Food and Drug Administration (FDA) on a number of occasions over the past 18 months to discuss conceptual, methodological, and clinical issues associated with PROs. Joyce Cramer, Pennifer Erickson, Paul Kind, and Nancy Kline Leidy have been serving as ISPOR’s representatives in these discussions, although many of those attending are also members of the ISPOR. Dr. Leidy has also been serving as ISPOR’s representative to the planning committee.

The most recent harmonization meeting, held at the U.S. Food and Drug Administration (FDA) on February 16, 2001, was titled “Issues in Patient-Reported Outcomes (PRO) Research”. The purpose of this meeting was to clarify terminology and concepts related to PROs, address methodological issues underlying the science of PRO evaluation, and discuss how, where, and why PROs can add value to clinical efficacy endpoints.

The four presentations were:
Conceptual and Definitional Issues
Team Leader: Margaret Rothman, Ph.D. Executive Director HE&P PGSM, RW Johnson Pharmaceutical Research Institute; Team Members: Ivan Barovsky PhD, Pennifer Erickson PhD, Paul Kind, M.Phil, Donald Patrick PhD, MSPH.

This presentation addressed the conceptual underpinnings of patient outcome assessment, including health-related quality of life and PROs.

The Value of Patient-Reported Outcomes
Team Leader: Nancy Kline Leidy, Ph.D., Vice President & Director of the Center for Health Outcomes Research, MEDTAP International, Inc. Team Members: Asha Hareendran, MD, Charlotte McMillan PhD, David Miller, PhD, Dennis Revicki PhD, Pierre Sagnier MD, Ingela Wiklund PhD

This presentation discussed the importance of the patient’s perspective and the uses of PROs in research and practice, including: PROs as an indication of disease; their use in evaluating treatment efficacy and interpreting clinical outcomes; and PRO data as key elements in treatment decision making.

Methodological Considerations in Obtaining PROs in Clinical Trials
Team Leader: Nancy Santanello, M.D., M.S., Senior Director, Epidemiology, Merck Research Laboratories; Team Members: Olivier Chassany MD, Dominique Dubois MD, Joseph Jackson PhD, Patrick Marquis MD, Rhys Williams PhD.

The underpinnings of PRO as a scientific discipline, and its use in clinical trials were addressed in this presentation.

Interest and Demand for PRO Information
Team Leader: Rick Berzon, Ph.D., Director, Corporate Health Economics, Boehringer Ingelheim Pharmaceuticals, Inc.; Team Members: Joyce Cramer, MA, Greg Boyer PhD, Haim Erder PhD, Albert Wu MD, PhD, Jean-Paul Gagnon PhD, Richard Wilke PhD

This presentation summarized evidence of the interest in and demand for PRO information on the part of patients, with recognition by clinicians of the value of patient evaluation and involvement.

Each presentation was followed by discussion between the harmonization group and FDA staff members. The inclusion of PROs (such as global impression, functional status, well-being symptoms, HRQL, satisfaction with treatment) in clinical trials was recognized as adding value for health care decision-making. The FDA indicated that a guidance on PRO issues is not planned for the near future. A manuscript summarizing the presentations at the February 2001 meeting is under development.

A subsequent meeting with the FDA is planned for September 21, 2001 at FDA headquarters. The issues to be discussed at this meeting are:
• 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

Further information about the harmonization efforts will
be presented during the ISPOR Fourth Annual European Congress, First Plenary Session.