Author Contributions: Drs Hatakeyama and Kawaoka had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Hatakeyama, Sugaya, Kawaoka.
Acquisition of data: Hatakeyama, Ito, Yamazaki, Ichikawa, Kimura, Kiso, Shimizu, Kawakami, Mitamura.
Analysis and interpretation of data: Hatakeyama, Koike, Kawaoka.
Drafting of the manuscript: Hatakeyama.
Critical revision of the manuscript for important intellectual content: Sugaya, Ito, Yamazaki, Ichikawa, Kimura, Kiso, Shimizu, Kawakami, Koike, Mitamura, Kawaoka.
Statistical analysis: Hatakeyama.
Obtained funding: Kawaoka.
Administrative, technical, or material support: Sugaya.
Study supervision: Kawaoka.
Financial Disclosures: Dr Kawaoka reports receiving speakers' honoraria from Chugai Pharmaceuticals, Novartis, Sankyo, Toyama Chemical, and Wyeth, and grant support from Chugai Pharmaceuticals, Daiichi Pharmaceutical, Sankyo, and Toyama Chemical. Dr Sugaya reports receiving speakers' honoraria from Chugai Pharmaceuticals, Sankyo Pharmaceuticals, and Takeda. Dr Koike reports receiving grant support from Chugai Pharmaceuticals. The information described in this article has been included in a patent application for novel amino acid substitutions found to affect sensitivity to neuraminidase inhibitors, compositions containing these substitutions, and methods for detecting them. No other disclosures were reported.
Funding/Support: This work was supported by grants from Core Research for Evolutional Science and Technology (CREST), Japan; grants from the Japan Science and Technology Agency (JST); grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labor and Welfare, Japan; and grants from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The oseltamivir carboxylate used in the study was provided by Roche Products.
Role of the Sponsors: None of the funding sources had any role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript.
Acknowledgment:We thank biostatistician Hiroshi Ohtsu, MS (Department of Clinical Bioinformatics, University of Tokyo), for his advice on the statistical analyses. We thank Larisa Gubareva, PhD (Department of Internal Medicine, University of Virginia Health Sciences Center), for providing us with a protocol for the sialidase inhibition assay, John Gilbert, BS (self-employed), for editing the manuscript, and Krisna Wells, BS, RN (University of Wisconsin-Madison), for technical assistance. We also thank Hideo Cho, MD (Department of Pediatrics, Kawasaki Municipal Hospital, Kanagawa, Japan), for his supervision. None of those acknowledged received compensation with the exception of John Gilbert, who is contracted by and receives a monthly salary from Dr Kawaoka to provide editorial services.