Exploring Perceived Barriers and Facilitators for Implementing Acute Pain Clinical Trials: A Mixed-Methods Analysis of Ketamine Infusions for Sickle Cell Pain

Martha O Kenney,1 Alexander T Limkakeng,2 Timothy N Ochoa,3 Joacy G Mathias,4 Mitchell R Knisely,5 Francis Keefe6 1Division of Pediatric Anesthesiology, Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA; 2Department of Emergency Medicine, Duke University School of Medicine, Durham, NC, USA; 3Duke University School of Medicine, Durham, NC, USA; 4Division of Women’s and Population Health, Duke University School of Medicine, Durham, NC, USA; 5Duke University School of Nursing, Durham, NC, USA; 6Pain Prevention and Treatment Research Program, Department of Psychiatry and Behavioral Science, Duke University, Durham, NC, USACorrespondence: Martha O Kenney, Division of Pediatric Anesthesiology, Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA, Email [email protected]: Vaso-occlusive events (VOEs) are the primary cause of acute pain in individuals with sickle cell disease (SCD), where high-dose opioids are the current standard treatment. Ketamine, a non-opioid analgesic, holds potential for managing acute SCD due to its opioid-sparing properties. This study aimed to explore the barriers and facilitators to an inpatient clinical trial of ketamine infusion for treatment of acute SCD pain.Methods: A mixed-methods design integrated quantitative survey data from 70 sickle cell and emergency medicine clinicians with qualitative insights from 10 patient focus group participants. Survey responses (n = 77 total, including seven registered nurses) were analyzed descriptively and via Fisher’s exact and Mann–Whitney U-tests, while focus groups were thematically coded using themes from the Consolidated Framework for Implementation Research.Results: Clinicians showed varied comfort levels with ketamine, with significant differences between sickle cell and emergency medicine clinicians. Barriers to future trials included the lack of standardized protocols (50.6%) and providers’ attitudes regarding ketamine (32.5%). Patients cited trust in providers and potential health benefits as key facilitators but also expressed concerns about safety, confidentiality, and time commitment of trial participation.Conclusion: Successful implementation of inpatient trials of pain interventions, such as ketamine infusions, requires a multidisciplinary approach, transparent communication about risks, strong clinical frameworks, and patient-centered trial designs. While study limitations, such as potential selection bias and low survey response rate, should be considered, these findings provide actionable insights to guide the design of future clinical trials and improve non-opioid pain management for SCD.Keywords: sickle cell disease, acute pain, ketamine, clinical trial