Redefining Pain Episodes in Sickle Cell Disease

Sickle cell pain episodes are often defined in trials by healthcare utilization and single-score pain scales. But many episodes are managed entirely at home, invisible to utilization-based endpoints, and shaped by personal baseline, triggers, and lived context. The result: endpoints that under-capture pain burden and can obscure therapeutic benefit.

This case study shows how a patient- and expert-informed model development initiative reframed how sickle cell pain episodes can be defined, modeled, and measured across home and clinical settings.

Why Sickle Cell Pain Episodes Defy Traditional Endpoints

Patient panelists consistently emphasized that pain in sickle cell disease is heterogeneous and context-dependent. Decisions to seek care were influenced not just by severity but by access, caregiving responsibilities, and prior experiences with clinicians. Panelists also described personal pain thresholds that traditional scales never register, thresholds that changed how the team thought about episode onset, escalation, and recovery.

A Patient-First Measurement Design

Across two sequential patient panels conducted with Alexion and the American Society of Hematology patient community, Koneksa developed a patient-defined episode model that challenges the assumption that sickle cell pain episodes are uniform, discrete events. The panels also produced clear, sometimes surprising feasibility findings on wearables, diaries, and PRO burden, including that 100% of panelists supported a disease-specific diary under one specific condition.