This issue of Value in Health includes articles resulting from an open-registration meeting organized jointly by the Mayo Clinic College of Medicine and the Food and Drug Administration (FDA) Center for Drug Evaluation and Research intended to facilitate review and discussion of the draft guidance document among diverse stakeholders and FDA representatives. The meeting, titled “FDA Guidance on Patient-Reported Outcomes: Discussion, Dissemination, and Operationalization,” was held during February 23–25, 2006, in Chantilly, VA, USA.
From this meeting, the FDA representatives were clear in that the guidance document was intended to be just that: guidance on how the FDA currently evaluates patient-reported outcomes (PROs) used as efficacy end points in support of labeling claims. The guidance is neither a statute nor a regulation nor inflexible over time as the science of PROs evolves. It was intentionally concise without discussion of specific methods or identification of acceptable PRO assessments to avoid being prescriptive.
Some participants during the meeting felt that the draft guidance document “set the bar too high” in terms of setting unrealistic expectations for PROs (in other words, the draft guidance document could hinder the inclusion of PRO end points in labeling claims because the “required” documentation of PRO development is just too extensive and/or expensive). Nevertheless, the FDA representatives again reiterated that the draft guidance document is not a strict guideline, but rather an effort to make clear how the FDA evaluates PROs in labeling claims. The FDA representatives took a very practical view in that via open, early, and continuing communication throughout the drug development process, drug developers should expect limited surprises in the FDA's review of the PRO end points in the labeling claim. Thus, a mantra for those intending to include PRO end points in a labeling claim should be, “Communication, communication, communication!”
The FDA representatives expressed a view that other end points will be and are being held to the same standard. For example, the FDA representatives expressed a view that items from the Common Terminology Criteria for Adverse Events  if used as efficacy end points would be scrutinized to the same extent as PRO end points. Further, although some historical clinical end points have known shortcomings and do not meet the level of validation suggested by the draft guidance document (e.g., tumor response) , new clinical end points will be held to the same expectation in terms of validation and interpretation. For example, in order to validate a new end point in adjuvant colon cancer clinical trials, Sargent et al.  performed a meta-analysis of patient-level data across 19 trials to compare the traditional end point of overall survival to the proposed new end point of disease-free survival. A similar analysis was undertaken by Ballman et al.  to assess the relationship between a new end point (6-month progression-free survival) and the traditional end point (12-month overall survival) in phase II clinical trials in patients with glioblastoma multiforme.
All in all, the FDA expects good science when it comes to PROs in labeling claims. The draft guidance document along with the articles of this issue provides a big step forward in presenting what is “good science” in PROs in labeling claims. Many of the challenges in PRO assessment have been identified and solutions presented (e.g., see Current Problems in Cancer) [6,7]. While meeting participants agreed on many issues, they disagreed on several others (e.g., whether anchor-based or distribution-based methods are better for determining the clinical significance of PRO changes, or whether all uncorrelated items should be equally weighted within a subscale). Fortunately, enough widely accepted methods (many presented in the articles of this issue) now exist so that PROs can be developed, applied, and interpreted with regularity and scientific integrity in clinical research and practice. With communication between drug developers and the FDA, PROs will continue to be successfully included in labeling claims.
For additional review of discussion during the meeting, see Dueck et al.