Study concept and design: Berk, Suhr, Sekijima, Zeldenrust, Yamashita, Nordh, Colton, Bisbee, Seldin, Merlini, Skinner, Kelly, Dyck.
Acquisition of data: Berk, Suhr, Obici, Sekijima, Zeldenrust, Heneghan, Litchy, Wiesman, Nordh, Corato, Lozza, Cortese, Robinson-Papp, Bisbee, Ando, Ikeda, Skinner, Dyck.
Analysis and interpretation of data: Berk, Suhr, Sekijima, Gorevic, Litchy, Corato, Colton, Rybin, Bisbee, Seldin, Merlini, Dyck.
Drafting of the manuscript: Berk, Zeldenrust, Yamashita, Heneghan, Colton, Rybin, Bisbee, Ando, Skinner, Dyck.
Critical revision of the manuscript for important intellectual content: Berk, Suhr, Obici, Sekijima, Zeldenrust, Gorevic, Litchy, Wiesman, Nordh, Corato, Lozza, Cortese, Robinson-Papp, Bisbee, Ikeda, Seldin, Merlini, Skinner, Kelly, Dyck.
Statistical analysis: Berk, Colton, Rybin, Bisbee.
Obtained funding: Berk, Nordh, Colton, Bisbee, Ando, Kelly.
Administrative, technical, or material support: Berk, Suhr, Obici, Sekijima, Yamashita, Heneghan, Litchy, Wiesman, Nordh, Bisbee, Seldin, Skinner, Dyck.
Study supervision: Berk, Litchy, Bisbee, Ikeda, Merlini, Dyck.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Berk, Obici, Zeldenrust, Litchy, and Dyck have received honoraria from Alnylam, ISIS, and Pfizer Pharmaceuticals. Dr Suhr has received support from Pfizer for activities as chairman of the Transthyretin Amyloidosis Outcome Survey (THAOS), ISIS, and Alnylam Pharmaceuticals. Dr Merlini has received honoraria from Pfizer. Dr Kelly reports financial holdings in FoldRx Pharmaceuticals Inc. No other disclosures were reported.
Diflunisal Consortium Members: Department of Medicine, Brigham and Womens Hospital, Boston, Massachusetts (Rodney H. Falk, MD); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota (Fletcher A. Miller Jr, MD); Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan (Yoko Horibata, MD); Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan (Jun Koyama, MD, PhD, and Hiroshi Morita, MD, PhD); Department of Internal Medicine, Fondazione Policlinico IRCCS San Matteo, University of Pavia, Pavia, Italy (Stefano Perlini, MD, PhD); Department of Cardiology, Umea University, Umea, Sweden (Per Lindqvist, PhD); Peripheral Nerve Center, Mayo Clinic Rochester, Rochester, Minnesota (Jenny Davies, BA); Department of Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden (Victoria Heldestad, PhD); Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden (Christina Frykolm, RN, and Hans-Erik Lundgren, RN); Peripheral Nerve Center and Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota (Karen Lodermeier, AA, Paula Orr, CCRA, and Melanie Thompson, CRC).
Funding/Support: This work was supported by grants from the National Institute of Neurological Diseases and Stroke (grant R01-NS051306), the Orphan Products Division of the US Food and Drug Administration (grant FD-R-002532), the Young Family Amyloid Research Fund, and the National Center for Advancing Translational Sciences, National Institutes of Health (grant UL1-TR000157). Merck Sharp and Dohme Inc supplied study drug (diflunisal).
Role of the Sponsor: National Institute of Neurological Disorders and Stroke representatives approved the trial design and appointed the data and safety monitoring board. Merck Sharp and Dohme Inc had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Disclaimer: The authors are solely responsible for the content of this article, which does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the Orphan Products Development Division of the US Food and Drug Administration.
Additional Contributions: We thank the patients participating in the study and their families; members of the data and safety monitoring board (Carol K. Redmond, PhD [chairperson], Anthony A. Amato, MD, Merrill D. Benson, MD, and Maria M. Picken, MD); Joel N. Buxbaum, MD (medical monitor); Elizabeth A. Hankinson, MPH (administrative core study coordinator); Susan S. Fish, PharmD, MPH (Boston University Medical Center Institutional Review Board chair emerita); National Institute of Neurological Diseases and Stroke officers Robin Conwit, MD, and Peter R. Gilbert, ScM; and the staffs of the Orphan Products Division of the US Food and Drug Administration, the Peripheral Nerve Center of Mayo Clinic, and the Data Coordinating Center at Boston University School of Public Health. None of these individuals received compensation for their contributions to this study.