Ethics approval and consent to participate
The study was approved by the Institutional Review Boards of all participating institutions and was performed in accordance with the Declaration of Helsinki, the International Conference on Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Good Clinical Practice, and local laws. All patients provided written informed consent. The trial is registered with the Japan Registry of Clinical Trials (JRCT) as trial number 031180136, and the University Hospital Network (UMIN) as trial number 000017877.
Consent to publish
Availability of data and materials
The datasets used and/or analysed during the current study are available on reasonable request from the corresponding author.
O.Y. reports honoraria from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Taiho Pharmaceutical Co., Ltd., MSD, Chugai Pharmaceutical Co., Ltd., and AstraZeneca. S.S. reports honoraria from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca, Chugai Pharmaceutical Co., Ltd., MSD, Bristol-Myers Squibb, Ono Pharmaceutical Co., Ltd., Eli Lilly and Company, Pfizer, Novartis, Taiho Pharmaceutical Co., Ltd., and Kyowa Hakko Kirin Co., Ltd. S.W. reports honoraria from Eli Lilly and Company, Pfizer, Novartis, AstraZeneca, Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Ono Pharmaceutical Co., Ltd., Daiichi Sankyo and Taiho Pharmaceutical Co., Ltd. M.M. reports honoraria from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, MSD, Novartis Pharma, Ono Pharmaceutical Co., Ltd. and Taiho Pharmaceutical Co., Ltd. O.H. reports honoraria from AstraZeneca, Boehringer Ingelheim and Novartis, and grants or funds from GlaxoSmithKline, AstraZeneca, Novartis, Bayer Health Care, Boehringer Ingelheim and Daiichi Sankyo. S.M. reports honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co., Ltd., Eli Lilly Japan, MSD, Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Taiho Pharmaceutical Co. Ltd., and research funding to their institution from Nippon Boehringer Ingelheim Co., Ltd. K.K. reports honoraria (speech fees) from AstraZeneca, Boehringer Ingelheim, Bristrol-Myers Squibb, Pfizer, Eli Lilly and Company, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co. and Ono Pharmaceutical Co., Ltd. A.G. reports honoraria from Boehringer Ingelheim. Y.M., S.K. K.U. and T.N. declare no conflict of interest.
Nippon Boehringer Ingelheim Co. Ltd funded the study but were not involved in the development of the manuscript.
Y.M. contributed to study design, data acquisition, data analysis and interpretation, and manuscript preparation and review. O.Y., S.S., S.K., S.W., K.U., M.M. and O.H. contributed to data acquisition and manuscript review. T.N. contributed to study design and manuscript review. S.M. contributed to study design, statistical analysis and manuscript review. K.K. contributed to data acquisition, quality control of data and algorithms, and manuscript review. A.G. contributed to study concept and design, and manuscript editing and review. All authors approved the final version of the manuscript, and agree to be accountable for all aspects of the work.
The authors would like to thank all patients, their families, coordinators and investigators involved in this study. We also thank Hiromi Odagiri and Yukio Kakehashi (North-East Japan Study Group, Saitama, Japan) for their technical support. Independent data management and statistical analysis was entrusted to AC Medical INC. Tokyo, Japan (coordinated by Eisei Oda). Medical writing assistance funded by Boehringer Ingelheim was provided by Fiona Scott, contracted by GeoMed, an Ashfield company, part of UDG Healthcare plc, during the preparation of this article.
1Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 113-8603 1-1-5 Sendagi Bunkyo-Ku, Tokyo, Japan
2Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397 Yamane, Hidaka City, Saitama, 350-1298 Japan
3Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai, 980-0873, Japan
4Department of Respiratory Medicine, National Hospital Organization, Iwakuni Clinical Center, 1-1-1 Atago Cyo Iwakuni City, Yamaguchi Prefecture 740-8510, Japan
5Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuouku, Niigata, 951-8510, Japan
6Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashigotanda Shinagawa Tokyo, Japan
7Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka City, Osaka, 560-8552 Japan
8Respiratory Center, Matsusaka Municipal Hospital, 1550 Tonomachi Matsusaka City, Mie, 515-8544 Japan
9Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 Japan
10Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan