Adam Wanner, MD,1 Stephen C. Groft, PharmD,2 J. Russell Teagarden, DMH, MA,3 Jeffrey Krischer, PhD,4 Barry R. Davis, MD, PhD,5 Christopher S. Coffey, PhD,6 David H. Hickam, MD, MPH,7 Jeffrey Teckman, MD,8 David R. Nelson, MD,9 Michael L. McCaleb, PhD,10 Rohit Loomba, MD, MHSc,11 Charlie Strange, MD,12 Robert A. Sandhaus, MD, PhD,13 Mark Brantly, MD,14 Jonathan M. Edelman, MD,15 Albert Farrugia, PhD16
Author Affiliations
- Division of Pulmonary and Critical Care Medicine, University of Miami and Alpha-1 Foundation, Miami, Florida
- National Institutes of Health, National Center for Advancing Translational Science, Office of Rare Diseases Research, Bethesda, Maryland[retired]
- National Organization of Rare Disorders, Danbury, Connecticut
- Rare Diseases Clinical Research Network, Data Management and Coordinating Center, University of South Florida, Tampa
- Department of Biostatistics, School of Public Health, University of Texas, Health Science Center, Houston
- Department of Biostatistics, College of Public Health, University of Iowa, Iowa City
- Program on the Assessment of Prevention, Diagnosis and Treatment, Patient-Centered Outcomes Research Institute, Washington, DC
- Division of Gastroenterology and Hepatology, Department of Pediatrics, School of Medicine, St. Louis University, Cardinal Glennon Children’s Medical Center, St. Louis, Missouri
- Clinical and Translational Science Institute, University of Florida, Gainesville
- Isis Pharmaceuticals, Carlsbad, California
- Division of Gastroenterology, Department of Medicine, Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego
- Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston
- Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado; Alpha-Net, Alpha-1 Foundation, Miami, Florida
- Division of Pulmonary and Critical Care Medicine, University of Florida, Gainesville
- Clinical Research & Development, CSL Behring, King of Prussia, Pennsylvania
- School of Surgery, University of Western Australia, Crawley
Address correspondence to:
Adam Wanner, MD
Division of Pulmonary and Critical Care Medicine
University of Miami
Miami, Florida
email: awanner@miami.edu
Abstract
Clinical research in rare diseases, including alpha-1 antitrypsin deficiency (AATD), faces challenges not shared by common disease research. These challenges may include the limited number of patient volunteers available for research, lack of natural history studies on which to base many clinical trial interventions, an urgency for the development of drug therapies given the often poor prognosis of rare diseases and uncertainties about appropriate biomarkers and clinical outcomes critical to clinical trial design. To address these challenges and initiate formal discussions among key stakeholders—patients, researchers, industry, federal regulators—the Alpha-1 Foundation hosted the Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases conference February 3-4, 2014 in Bethesda, Maryland. Discussions at the conference led to the conclusions that 1) adaptive designs should be considered for rare disease clinical trials yet more dialogue and study is needed to make these designs feasible for smaller trials and to address current limitations; 2) natural history studies, including the identification of appropriate biomarkers are critically needed and precompetitive collaborations may offer a means of creating these costly studies; and 3) patient registries and databases within the rare disease community need to be more publicly available and integrated, particularly for AATD. This report summarizes the discussions leading to these conclusions.
Citation
Citation: Wanner A, Groft SC, Teagarden JR, et al. Clinical trial design for alpha-1 antitrypsin deficiency: A model for rare diseases. J COPD F. 2015; 2(2): 177-190. doi: http://doi.org/10.15326/jcopdf.2.2.2015.0132