STArT Investigator Explains Why Sickle Cell Pain Outcomes Vary Across Patients and Hospitals

In an interview with Pharmacy Times, Claudia R. Morris, MD, lead investigator and author of the phase 3 Sickle Cell Disease Treatment With Arginine Therapy (STArT) trial and a pediatric emergency medicine physician at Children’s Healthcare of Atlanta, discussed how patient history and institutional pain-management practices may influence time to crisis resolution and how care teams, including pharmacists, can help standardize treatment.

An analysis of the placebo arm found that prior surgery and having no recent emergency department visits that ended in discharge were independently associated with longer time to crisis resolution. Morris explains that the latter finding did not indicate lower emergency department use. Instead, these patients were admitted whenever they sought emergency care, potentially reflecting a more severe disease or pain phenotype. Previous splenectomy or cholecystectomy could similarly indicate more severe hemolytic disease. However, the association also included minor procedures, raising the possibility that painful experiences earlier in life may contribute to hyperalgesia and shape future pain responses.

Morris also examines the variation observed among hospitals. Although time to crisis resolution has some biological relevance, it is affected by differences in analgesic use, opioid discontinuation, clinician behavior, and barriers that influence when patients reach the emergency department. These influences make it difficult to determine whether the end point reflects a treatment’s biological effect or institutional practice.

More objective measures may therefore be needed. Morris identifies oxidative stress, inflammation, mitochondrial function, and hemolysis as potential areas for investigation, while emphasizing that end points for preventive studies should differ from those used in acute emergency care.

Patient-reported outcomes present another challenge because instruments ask patients to consider the preceding 7 days. Assessments conducted at discharge may capture hospitalization, pain, disrupted sleep, and blood draws, causing scores to appear worse. In a STArT subgroup assessed 7 to 10 days after discharge, pain, pain intensity, and fatigue improved significantly from presentation, although the sample was too small to establish an arginine treatment effect.