End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings

Ann T Farrell¹, Julie Panepinto², Ankit A Desai³, Adetola A Kassim⁴, Jeffrey Lebensburger⁵, Mark C Walters⁶, Daniel E Bauer^{7

8

9}, Rae M Blaylark^{10

11}, Donna M DiMichele¹², Mark T Gladwin¹³, Nancy S Green¹⁴, Kathryn Hassell¹⁵, Gregory J Kato¹⁶, Elizabeth S Klings¹⁷, Donald B Kohn^{18

19

20}, Lakshmanan Krishnamurti²¹, Jane Little²², Julie Makani²³, Punam Malik^{24

25}, Patrick T McGann^{24

25}, Caterina Minniti²⁶, Claudia R Morris^{27

28}, Isaac Odame^{29

30}, Patricia Ann Oneal¹, Rosanna Setse¹, Poornima Sharma³¹, Shalini Shenoy³²

Affiliations

¹ US Food and Drug Administration, White Oak, MD.
² Pediatric Hematology, Medical College of Wisconsin/Children's Wisconsin, Milwaukee, WI.
³ Krannert Institute of Cardiology, Department of Medicine, Indiana University, Indianapolis, IN.
⁴ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
⁵ Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
⁶ UCSF Benioff Children's Hospital, Oakland, CA.
⁷ Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
⁸ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
⁹ Department of Pediatrics, Harvard Medical School, Boston, MA.
¹⁰ Children's Hospitals and Clinics of MN, Minneapolis, MN.
¹¹ Sickle Cell Foundation of Minnesota, Minneapolis, MN.
¹² National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
¹³ Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
¹⁴ Department of Pediatrics, Columbia University Medical Center, New York, NY.
¹⁵ Division of Hematology, Department of Medicine, University of Colorado, Aurora, CO.
¹⁶ Division of Hematology-Oncology and Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
¹⁷ The Pulmonary Center, Boston University School of Medicine, Boston, MA.
¹⁸ Department of Microbiology, Immunology & Molecular Genetics.
¹⁹ Department of Pediatrics, and.
²⁰ Department of Molecular & Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
²¹ Aflac Cancer and Blood Disorders Center, Emory University, Children's Healthcare of Atlanta, Atlanta, GA.
²² Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC.
²³ Department of Haematology and Blood Transfusion, School of Medicine, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania.
²⁴ Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
²⁵ Department of Pediatrics, University of Cincinnati, Cincinnati, OH.
²⁶ Division of Hematology, Montefiore Health System, Albert Einstein College of Medicine, New York, NY.
²⁷ Division of Pediatric Emergency Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
²⁸ Children's Healthcare of Atlanta, Atlanta, GA.
²⁹ The Hospital for Sick Children, Toronto, ON, Canada.
³⁰ University of Toronto, Toronto, ON, Canada.
³¹ Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD; and.
³² Division of Pediatric Hematology Oncology and Stem Cell Transplant, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.

PMID: 31809537
PMCID: PMC6963248
DOI: 10.1182/bloodadvances.2019000883

End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings

Ann T Farrell et al. Blood Adv. 2019.

. 2019 Dec 10;3(23):4002-4020.

doi: 10.1182/bloodadvances.2019000883.

Authors

Affiliations

¹ US Food and Drug Administration, White Oak, MD.
² Pediatric Hematology, Medical College of Wisconsin/Children's Wisconsin, Milwaukee, WI.
³ Krannert Institute of Cardiology, Department of Medicine, Indiana University, Indianapolis, IN.
⁴ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
⁵ Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
⁶ UCSF Benioff Children's Hospital, Oakland, CA.
⁷ Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA.
⁸ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
⁹ Department of Pediatrics, Harvard Medical School, Boston, MA.
¹⁰ Children's Hospitals and Clinics of MN, Minneapolis, MN.
¹¹ Sickle Cell Foundation of Minnesota, Minneapolis, MN.
¹² National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
¹³ Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
¹⁴ Department of Pediatrics, Columbia University Medical Center, New York, NY.
¹⁵ Division of Hematology, Department of Medicine, University of Colorado, Aurora, CO.
¹⁶ Division of Hematology-Oncology and Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
¹⁷ The Pulmonary Center, Boston University School of Medicine, Boston, MA.
¹⁸ Department of Microbiology, Immunology & Molecular Genetics.
¹⁹ Department of Pediatrics, and.
²⁰ Department of Molecular & Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
²¹ Aflac Cancer and Blood Disorders Center, Emory University, Children's Healthcare of Atlanta, Atlanta, GA.
²² Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC.
²³ Department of Haematology and Blood Transfusion, School of Medicine, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania.
²⁴ Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
²⁵ Department of Pediatrics, University of Cincinnati, Cincinnati, OH.
²⁶ Division of Hematology, Montefiore Health System, Albert Einstein College of Medicine, New York, NY.
²⁷ Division of Pediatric Emergency Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
²⁸ Children's Healthcare of Atlanta, Atlanta, GA.
²⁹ The Hospital for Sick Children, Toronto, ON, Canada.
³⁰ University of Toronto, Toronto, ON, Canada.
³¹ Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD; and.
³² Division of Pediatric Hematology Oncology and Stem Cell Transplant, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.

PMID: 31809537
PMCID: PMC6963248
DOI: 10.1182/bloodadvances.2019000883

Abstract

To address the global burden of sickle cell disease 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 outcome, pain (non-patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

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Conflict of interest statement

Conflict-of-interest disclosure: For full conflict-of-interest information, please see the supplemental disclosure file.

References

1. Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med. 2010;38(4 suppl):S512-S521. - PubMed
1. Farrell AT, Panepinto J, Carroll CP, et al. End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain. Blood Adv. 2019;3(23):3982-4001. - PMC - PubMed
1. FDA-NIH Biomarker Working Group BEST (Biomarkers, EndpointS, and other Tools) resource. Available at: https://www.ncbi.nlm.nih.gov/books/NBK326791/. Accessed 25 September 2019. - PubMed
1. Manci EA, Culberson DE, Yang YM, et al. ; Investigators of the Cooperative Study of Sickle Cell Disease . Causes of death in sickle cell disease: an autopsy study. Br J Haematol. 2003;123(2):359-365. - PubMed
1. Serjeant GR, Chin N, Asnani MR, et al. Causes of death and early life determinants of survival in homozygous sickle cell disease: the Jamaican cohort study from birth. PLoS One. 2018;13(3):e0192710. - PMC - PubMed

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End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings

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End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings

Authors

Affiliations

Abstract

Conflict of interest statement

References

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