PSY61 - Who told you that: Do guidelines for including patient-centered outcome measures in systemic lupus erythematosus clinical trials include patient input?

Abstract

The importance of patient-centered outcomes (PCO) in drug development is increasingly recognized by health authorities, clinical advisory and patient advocacy bodies. Accordingly, many of these organizations seek to include PCO in their guidelines and recommendations. However, complex disorders present measurement challenges that are difficult to resolve within the scope of a clinical trial (CT). An example is Systemic Lupus Erythematosus (SLE), characterized by myriad clinical indicator, symptom, severity and frequency combinations. SLE patient burden studies demonstrate that, while symptoms differ, the impact is universal. This study evaluates the relationship between recently updated SLE guidances and concepts reported directly by SLE patients. A qualitative study comprised of six SLE patient focus groups (N=43) was conducted to elicit direct patient input on key symptoms and concepts. FDA and EMA guidelines for SLE clinical trials, European League Against Rheumatism (EULAR) CT endpoint recommendations, and the Systemic Lupus International Collaborating Clinics (SLICC) classification system were evaluated for PCO-specific content. Patient-reported outcomes (PRO) concepts from the study were then compared to the PCO content from the guidelines and recommendations. All study subjects (mean age 44.3 years; 91.7% women; 63% diagnosed ≥ 5 years; 91% experienced flare ≤ 3 months; 74% mild/moderate disease) identified fatigue among “most important symptoms” with 98% citing pain and 44% fog/confusion. Regardless of “importance” all subjects deemed other symptoms highly disruptive. EMA and FDA both specify fatigue as a clinical trial endpoint. FDA included “fatigue” based on clinician input, but recommended development of a PRO-based fatigue exploratory endpoint. EULAR, citing challenges of symptom endpoints, suggested general Health-Related Quality of Life. The SLICC didn’t mention PCOs. Patients identified multiple SLE symptoms and impacts, yet guidances didn’t address these issues. Joint efforts between patients, sponsors, regulators and advisory organizations are necessary to implement relevant PCOs, especially in complex disorders.