Document is current

Article History

Accepted: 1 August 2025

First Online: 1 September 2025

Declarations

:

: No funding was received by the principal investigators for the conduct of this study or preparation of the manuscript. Effort of Stephen Crystal and Sharon Cook in analyses of US Medicaid data was supported in part by National Institute on Drug Abuse grants R01 DA047347 and R01 DA057568. The funding source had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit it for publication. No funding was received to cover open access fees.

: A.H.Y.C. received a Universitas 21 collaborative research grant to support the work reported in this paper. A.H.Y.C. reports a senior research fellowship from Auckland Medical Research Foundation and was the previous Robert Irwin Postdoctoral Fellowship awardee at the time this work was conducted. A.H.Y.C. has received consultancy fees from AcademeX and UCL-Business spin-out Spoonful of Sugar Ltd. A.H.Y.C. has also received research grants from Asthma UK, the University of Auckland, Health Research Council of New Zealand, Oakley Mental Health Foundation, Chorus Ltd, World Health Organisation, A+ Trust and Hong Kong University, outside this submitted work. A.H.Y.C. is also a Board member of Asthma NZ and member of Respiratory Effectiveness Group (REG). J.H. has received consultancy fees from Enigma Solutions Ltd. (New Zealand)—a clinical knowledge management and clinical expert system provider, Medsafe, the New Zealand Medicines and Medical Devices Safety Authority, Pharmaceutical Management Agency (a New Zealand crown entity), MIMS Pte Ltd (Singapore), Pall Corporation (New Zealand), and Sanofi (UK). J.H. has also received research grants from the University of Auckland, Health Research Council of New Zealand, Oakley Mental Health Foundation, National Heart Foundation (New Zealand), Health Workforce New Zealand, Tertiary Education Commission (New Zealand), A+ Trust and Hong Kong University, outside this submitted work. UH and OS are working at an independent, nonprofit research institute, the Leibniz Institute for Prevention Research and Epidemiology—BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. These are post-authorization safety studies (PASS) requested by health authorities. The design and conduct of these studies as well as the interpretation and publication are not influenced by the pharmaceutical industry. P.G.P. reported close family member interest—employee at TEVA. E.C.C.L. reports research funding outside the submitted work from Amgen, Pfizer, Sanofi, Takeda, Roche, IQVIA, the Taiwan National Science and Technology Council (ID:111-2628-B-006-007-), the Taiwan National Health Research Institutes. ØK and KF report participation in regulator-mandated post-authorization safety studies (PASS) of drugs with no relation to the work reported in this paper with funds paid to the institution where they are employed (no personal fees). W.C.Y.L. reports grant from AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. A.P. reports participation in research projects funded by Alcon, Almirall, Astellas, Astra-Zeneca, Boehringer-Ingelheim, Novo Nordisk, Servier and LEO Pharma, all regulator-mandated phase IV-studies, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this paper. Analyses of US Medicaid data were supported in part by NIDA grant 1R01 DA047347. KKCM is the recipient of the CW Maplethorpe Fellowship, reports grants from the European Union Horizon 2020, the UK National Institute of Health Research and the Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, and reports personal fees from IQVIA, unrelated to the submitted work. I.C.K.W. reports research funding from the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the National Institute for Health Research in England, the European Commission, IQVIA, Amgen and GSK, consulting fees from IQVIA and World Health Organization, outside of the submitted work. He is a nonexecutive director of Jacobson Medical, Advance Data Analytics for Medical Science (ADAMS) Limited in Hong Kong and OCUS Innovation Limited (HK, Ireland and UK); a former director of Therakind in England and Asia Medicine Regulatory Affairs (AMERA) Services Limited in Hong Kong. Lotte Rasmussen reports participation in research projects funded by Novo Nordisk with funds paid to the institution where she was employed (no personal fees) and with no relation to the work reported in this paper. H.Z. was supported by a UNSW Scientia Program Award during the conduct of this study. A.Y.L.C., S.B., K.B., G.B., B.C., S.C., S.Cr., S.G., R.G., S.Gi., C.H., H.L.J., J.K., J.H.K., K.K., H.L., K.L., E.L., G.M., A.N., V.P., N.Q., J.R., L.S., T.S., C.S.-V., C.-Y.S., J.-Y.S., T.S., K.T., M.T., S.W., and K.H.T.W.W. declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

: Each participating site followed the relevant local ethics and regulatory frameworks for study approval, namely, Australia: The External Requests Evaluation Committee (RMS0863); Canada: University of British Columbia Clinical Research Ethics Board (UW 19-762); Hong Kong: University of Hong Kong/ Hospital Authority Hong Kong West Cluster (UW20-051); Iceland: National Bioethics Committee (VSN-20-058); Norway: Regional Ethics Committee (REK) (REK sør-øst D, ref. 92144); New Zealand: Auckland Health Research Ethics Committee (26501); South Korea: Sungkyunkwan University Institutional Review Board (2019-05-006); Spain: CEIm-Regional de la Comunidad de Madrid (01/20); Taiwan: Taiwan National Cheng Kung University Hospital Institutional Review Board (A-ER-107-387); the United Kingdom: Independent Scientific Advisory Committee (19_169); and the United States: University of North Carolina Institutional Review Board (19-3195) and Rutgers, The State University of New Jersey ArtSci Institutional Review Board (Pro2020002048). Ethical approval is exempted in Denmark, Finland, France, Germany, Italy, the Netherlands, New Zealand, Sweden.

: Not applicable.

: Not applicable.

: I.C.K.W., K.K.C.M.

: I.C.K.W., K.K.C.M., and A.Y.L.C. had full access to the aggregate analysis data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. I.C.K.W. and K.K.C.M. were responsible for the study concept, and I.C.K.W., K.K.C.M., and A.Y.L.C. were responsible for the study design. All authors were involved in the acquisition, statistical analysis, or interpretation of data. I.C.K.W., K.K.C.M., and A.Y.L.C. drafted the manuscript. All authors critically revised the manuscript for important intellectual content.

: The aggregate-level datasets generated or analyzed during the current study are available from the corresponding author on reasonable request subject to agreement from the site-investigators and their respective data providers.

: R codes and dataset adopted in this study are available on GitHub repository at .