End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain.

Farrell AT1, Panepinto J2, Carroll CP3, Darbari DS4, Desai AA5, King AA6, Adams RJ7, Barber TD8, Brandow AM2, DeBaun MR9, Donahue MJ10,11,12, Gupta K13, Hankins JS14, Kameka M15, Kirkham FJ16,17, Luksenburg H18, Miller S19, Oneal PA1, Rees DC20,21, Setse R1, Sheehan VA22, Strouse J23,24, Stucky CL25, Werner EM18, Wood JC26, Zempsky WT27.

Author information

1: US Food and Drug Administration, White Oak, MD.
2: Pediatric Hematology, Medical College of Wisconsin/Children's Wisconsin, Milwaukee, WI.
3: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD.
4: Children's National Medical Center, Washington, DC.
5: Krannert Institute of Cardiology, Indiana University, Bloomington, IN.
6: Division of Hematology and Oncology in Pediatrics and Medicine, Washington University School of Medicine, St. Louis, MO.
7: Department of Neurology, Medical University of South Carolina, Charleston, SC.
8: Patient Advocate, Rochester, NY.
9: Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN.
10: Department of Radiology and Radiological Sciences.
11: Department of Neurology, and.
12: Department of Psychiatry, School of Medicine, Vanderbilt University, Nashville, TN.
13: Division of Hematology, Oncology, and Transplantation, Department of Medicine, Medical School, University of Minnesota, Minneapolis, MN.
14: Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN.
15: Nicole Wertheim College of Nursing and Health Sciences, Florida International University, Miami, FL.
16: Developmental Neurosciences Unit and.
17: Biomedical Research Unit, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
18: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
19: Atrium Healthcare, Charlotte, NC.
20: Department of Haematological Medicine, King's College Hospital, London, United Kingdom.
21: School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.
22: Division of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
23: Division of Hematology, Department of Medicine, and.
24: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Duke University School of Medicine, Durham, NC.
25: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI.
26: Children's Hospital Los Angeles, Los Angeles, CA; and.
27: Department of Pediatrics, Connecticut Children's/School of Medicine, University of Connecticut, Hartford, CT.

Abstract

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.