Are Sickle Cell Pain Trials Measuring the Wrong Outcomes—and How Can Pharmacists Help?

In an interview with Pharmacy Times, Claudia R. Morris, MD, lead investigator and author of the phase 3 STArT trial and a pediatric emergency medicine physician at Children’s Healthcare of Atlanta, discussed the need for more meaningful end points in sickle cell pain trials, future research targeting acute chest syndrome, and how pharmacists can improve the collection of opioid-use data.

Morris explained that research networks such as the Pediatric Emergency Care Applied Research Network (PECARN) have helped overcome longstanding enrollment challenges in sickle cell disease studies. STArT enrolled 274 participants within approximately 3 years and remained ahead of schedule. However, the trial’s substantial variability suggested that more than 900 participants would have been required to detect the originally anticipated 17-hour difference in time to crisis resolution. That enrollment target would be difficult to achieve in a rare disease population.

According to Morris, time to crisis resolution and hospital length of stay are heavily influenced by institutional practices, including decisions surrounding opioid discontinuation and discharge. Continuing to rely on these measures could prevent investigators from accurately determining whether therapies affect the underlying biology of vaso-occlusive pain. She called for collaboration among investigators, patients, regulators, and other stakeholders to identify and validate more meaningful clinical end points or surrogate biomarkers acceptable to the FDA.

Although STArT did not provide a definitive answer regarding arginine therapy, Morris noted an exploratory signal among participants with acute chest syndrome. She is working with PECARN to design a study focused on this complication. Because patients with acute chest syndrome generally remain hospitalized longer and have evidence of vaso-occlusion, time to crisis resolution or hospital length of stay may be more informative in this population.

Morris also identified an opportunity for pharmacists to strengthen future research. Investigators had difficulty determining participants’ total parenteral opioid exposure because research coordinators had to reconstruct doses from patient-controlled analgesia settings, infusion duration, and bolus administration. She urged pharmacy departments to develop reliable methods for reporting the exact amount of opioids administered each day. More accessible, validated medication-use data could reduce calculation errors and improve the accuracy of opioid-related outcomes in future trials.