The document summarizes key points from an FDA guidance on patient-reported outcomes (PROs) and the use of electronic PROs (ePROs). It defines PROs as measures coming directly from patients about their health without interpretation. The FDA guidance provides recommendations on PRO development, validation and use in clinical trials to support product labels. It also discusses levels of evidence needed to establish equivalence when migrating paper PROs to electronic formats, with more changes requiring more rigorous validation. In general, studies show high correlations and equivalence between paper and ePRO versions.

1. FDA Guidance on PROs Breakfast Seminar 19 th March 2009 Diane Wild, MSc Oxford Outcomes Ltd., Oxford, UK

10. Copyright ©1996 BMJ Publishing Group Ltd. Hickey, A. M et al. BMJ 1996;313:29-33 Fig 1--The segments represent five areas of life nominated by the individual; the size of the segment can be adjusted to show the relative importance of each area for the individual's quality of life

12. HRQL of Patients with COPD vs. General Population Norms (SF-36) High scores = good HRQL

13. FDA Draft Guidance

16. Assess Measurement Properties Assess score reliability, validity and ability to detect change. Evaluate administrative & respondent burden. Add, delete or revise items. Identify meaningful differences in scores. Finalise instrument formats, scoring, procedures & training materials. From FDA Draft PRO Guidance document 2006 Identify Concepts & Develop Conceptual Framework Identify concepts & domains that are important to patients. Determine intended population and research application. Hypothesize expected relationships among concepts. Create Instrument Generate items. Choose administration method, recall period & response scales. Draft instructions. Format instrument. Draft procedures for scoring & administration. Pilot test draft instrument. Refine instrument & procedures. Modify Instrument Change concepts measured, populations studied, research application, response options, recall period or method of administration. PRO

20. PRO Review on Critical Path Preclinical Phase 2A Phase 2B Phase 3 Phase I Pre-IND EOP2B EOP2A EOP1 Initial PRO Submission (Updated) PRO submission Submit Final PRO Evidence Dossier PRO Selection/ Development PRO Validation/ Modification

21. Approved Product Labels Label Claims Based on Patient-Reported Outcomes in EMEA and FDA Approvals Since 2000 Jane Scott etal. Poster presented at ISPOR Athens 2008 37.8 8.9 7.6 3.4 85.6 17.6 16.1 1.1 8.5 yr Mean 331 76 65 29 728 150 137 9 Total 26 4 4 2 34 4 4 0 2008* 69 13 13 7 75 14 11 1 2007 42 5 5 0 98 18 15 4 2006 23 7 7 3 82 15 13 1 2005 36 11 8 6 114 23 20 0 2004 18 9 6 2 79 18 17 1 2003 38 10 10 0 79 15 14 1 2002 38 13 11 6 71 18 18 1 2001 31 4 1 3 96 25 25 0 2000 All Approvals Any PRO Signs & Symptoms HRQL All Approvals Any PRO Signs & Symptoms HRQL Year EMEA Approvals by Year FDA Approvals by Year PRO Claims in FDA and EMEA Product Labels Approved between 1 January 2000 and 2 June 2008

22. ePRO migration:level of evidence required to establish equivalence