{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:46:32Z","timestamp":1791953192396,"version":"4.3.4"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Ther"],"DOI":"10.1007\/s40120-026-01043-6","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:39:44Z","timestamp":1791031184000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time Course of Rimegepant Effect for Acute Treatment of Migraine in Adults Unsuitable for Triptans: Exploratory Endpoints from a Phase 4, Randomized, Double-Blind, Placebo-Controlled Study"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6717-9234","authenticated-orcid":false,"given":"Michel","family":"Lanteri-Minet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2932-0115","authenticated-orcid":false,"given":"Catherine","family":"Nalpas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz M.","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Thiry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannin","family":"McCollum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9639-7918","authenticated-orcid":false,"given":"Sara","family":"Ramaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-1248","authenticated-orcid":false,"given":"Robert","family":"Fountaine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"issue":"8","key":"1043_CR1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024241252666","volume":"44","author":"F Puledda","year":"2024","unstructured":"Puledda F, Sacco S, Diener HC, et al. International Headache Society global practice recommendations for the acute pharmacological treatment of migraine. Cephalalgia. 2024;44(8):3331024241252666.","journal-title":"Cephalalgia"},{"issue":"7","key":"1043_CR2","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1111\/head.14153","volume":"61","author":"J Ailani","year":"2021","unstructured":"Ailani J, Burch RC, Robbins MS, Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021\u201339.","journal-title":"Headache"},{"issue":"1","key":"1043_CR3","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1111\/head.14854","volume":"65","author":"RB Lipton","year":"2025","unstructured":"Lipton RB, Gendolla A, Abraham L, et al. Relative frequency, characteristics, and disease burden of patients with migraine unsuitable for triptan treatment: a systematic literature review. Headache. 2025;65(1):164\u201379.","journal-title":"Headache"},{"issue":"12","key":"1043_CR4","doi-asserted-by":"publisher","first-page":"4765","DOI":"10.1007\/s12325-020-01494-9","volume":"37","author":"E Leroux","year":"2020","unstructured":"Leroux E, Buchanan A, Lombard L, et al. Evaluation of patients with insufficient efficacy and\/or tolerability to triptans for the acute treatment of migraine: a systematic literature review. Adv Ther. 2020;37(12):4765\u201396.","journal-title":"Adv Ther"},{"issue":"1","key":"1043_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01676-0","volume":"24","author":"R Ruscheweyh","year":"2023","unstructured":"Ruscheweyh R, Gossrau G, Dresler T, et al. Triptan non-response in specialized headache care: cross-sectional data from the DMKG Headache Registry. J Headache Pain. 2023;24(1):135.","journal-title":"J Headache Pain"},{"issue":"1","key":"1043_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-022-01502-z","volume":"23","author":"S Sacco","year":"2022","unstructured":"Sacco S, Lampl C, Amin FM, et al. European Headache Federation (EHF) consensus on the definition of effective treatment of a migraine attack and of triptan failure. J Headache Pain. 2022;23(1):133.","journal-title":"J Headache Pain"},{"issue":"1","key":"1043_CR7","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s40122-020-00223-y","volume":"10","author":"K Hirata","year":"2021","unstructured":"Hirata K, Ueda K, Komori M, et al. Unmet needs in Japanese patients who report insufficient efficacy with triptans for acute treatment of migraine: retrospective analysis of real-world data. Pain Ther. 2021;10(1):415\u201332.","journal-title":"Pain Ther"},{"issue":"1","key":"1043_CR8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s10194-020-01110-9","volume":"21","author":"L Lombard","year":"2020","unstructured":"Lombard L, Farrar M, Ye W, et al. A global real-world assessment of the impact on health-related quality of life and work productivity of migraine in patients with insufficient versus good response to triptan medication. J Headache Pain. 2020;21(1):41.","journal-title":"J Headache Pain"},{"issue":"6","key":"1043_CR9","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1111\/head.12820","volume":"56","author":"M Fischer","year":"2016","unstructured":"Fischer M, Frank F, Wille G, Klien S, Lackner P, Broessner G. Triptans for acute migraine headache: current experience with triptan use and prescription habits in a tertiary care headache outpatient clinic: an observational study. Headache. 2016;56(6):952\u201360.","journal-title":"Headache"},{"issue":"1-2","key":"1043_CR10","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.jns.2012.12.020","volume":"326","author":"S Holland","year":"2013","unstructured":"Holland S, Fanning KM, Serrano D, Buse DC, Reed ML, Lipton RB. Rates and reasons for discontinuation of triptans and opioids in episodic migraine: results from the American Migraine Prevalence and Prevention (AMPP) study. J Neurol Sci. 2013;326(1\u20132):10\u20137.","journal-title":"J Neurol Sci"},{"issue":"2","key":"1043_CR11","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1111\/head.12198","volume":"54","author":"RE Wells","year":"2014","unstructured":"Wells RE, Markowitz SY, Baron EP, et al. Identifying the factors underlying discontinuation of triptans. Headache. 2014;54(2):278\u201389.","journal-title":"Headache"},{"issue":"1","key":"1043_CR12","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s40120-021-00304-w","volume":"11","author":"A Gendolla","year":"2022","unstructured":"Gendolla A, Rauer N, Kraemer S, Schwerdtner I, Straube A. Epidemiology, demographics, triptan contraindications, and prescription patterns of patients with migraine: a German claims database study. Neurol Ther. 2022;11(1):167\u201383.","journal-title":"Neurol Ther"},{"issue":"1","key":"1043_CR13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1111\/head.12962","volume":"57","author":"DC Buse","year":"2017","unstructured":"Buse DC, Reed ML, Fanning KM, Kurth T, Lipton RB. Cardiovascular events, conditions, and procedures among people with episodic migraine in the US population: results from the American Migraine Prevalence and Prevention (AMPP) study. Headache. 2017;57(1):31\u201344.","journal-title":"Headache"},{"key":"1043_CR14","doi-asserted-by":"publisher","DOI":"10.1177\/2150132720963680","volume":"11","author":"DW Dodick","year":"2020","unstructured":"Dodick DW, Shewale AS, Lipton RB, et al. Migraine patients with cardiovascular disease and contraindications: an analysis of real-world claims data. J Prim Care Community Health. 2020;11:2150132720963680.","journal-title":"J Prim Care Community Health"},{"issue":"1","key":"1043_CR15","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s10194-025-02086-0","volume":"26","author":"M Lanteri-Minet","year":"2025","unstructured":"Lanteri-Minet M, Casarotto C, Bretin O, et al. Prevalence, characteristics and management of migraine patients with triptan failure in primary care: the EMR France-Mig study. J Headache Pain. 2025;26(1):153.","journal-title":"J Headache Pain"},{"issue":"6","key":"1043_CR16","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1080\/14737175.2022.2091435","volume":"22","author":"AA Argyriou","year":"2022","unstructured":"Argyriou AA, Mantovani E, Mitsikostas DD, Vikelis M, Tamburin S. A systematic review with expert opinion on the role of gepants for the preventive and abortive treatment of migraine. Expert Rev Neurother. 2022;22(6):469\u201388.","journal-title":"Expert Rev Neurother"},{"issue":"12","key":"1043_CR17","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1080\/14737175.2024.2434079","volume":"24","author":"L Edvinsson","year":"2024","unstructured":"Edvinsson L. Rimegepant for the acute and preventive treatment of migraine: a narrative review of the evidence. Expert Rev Neurother. 2024;24(12):1141\u201355.","journal-title":"Expert Rev Neurother"},{"issue":"1","key":"1043_CR18","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1097\/WNF.0000000000000576","volume":"47","author":"C Yang","year":"2024","unstructured":"Yang C, Zhang Y. Efficacy and safety of rimegepant for migraine patients: a meta-analysis of randomized controlled studies. Clin Neuropharmacol. 2024;47(1):7\u201311.","journal-title":"Clin Neuropharmacol"},{"key":"1043_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1205778","volume":"14","author":"Q Wang","year":"2023","unstructured":"Wang Q, Wang S, Zhu Y, Lin F. Clinical efficacy and safety of rimegepant in the treatment of migraine: a meta-analysis of randomized controlled trials. Front Neurol. 2023;14:1205778.","journal-title":"Front Neurol"},{"issue":"3","key":"1043_CR20","doi-asserted-by":"publisher","DOI":"10.1177\/03331024231151419","volume":"43","author":"F Puledda","year":"2023","unstructured":"Puledda F, Younis S, Huessler EM, et al. Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: a systematic review and network meta-analysis of the literature. Cephalalgia. 2023;43(3):3331024231151419.","journal-title":"Cephalalgia"},{"issue":"3","key":"1043_CR21","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1111\/head.14089","volume":"61","author":"AM Blumenfeld","year":"2021","unstructured":"Blumenfeld AM, Goadsby PJ, Dodick DW, et al. Efficacy of ubrogepant based on prior exposure and response to triptans: a post hoc analysis. Headache. 2021;61(3):422\u20139.","journal-title":"Headache"},{"issue":"2","key":"1043_CR22","doi-asserted-by":"publisher","DOI":"10.1177\/03331024221141686","volume":"43","author":"RB Lipton","year":"2023","unstructured":"Lipton RB, Blumenfeld A, Jensen CM, et al. Efficacy of rimegepant for the acute treatment of migraine based on triptan treatment experience: pooled results from three phase 3 randomized clinical trials. Cephalalgia. 2023;43(2):3331024221141686.","journal-title":"Cephalalgia"},{"issue":"11","key":"1043_CR23","doi-asserted-by":"publisher","DOI":"10.1177\/03331024251395298","volume":"45","author":"M Ashina","year":"2025","unstructured":"Ashina M, McAllister P, Gaul C, et al. Rimegepant for acute treatment of migraine in triptan-unsuitable adults: a randomized, double-blind, placebo-controlled phase 4 trial. Cephalalgia. 2025;45(11):3331024251395298.","journal-title":"Cephalalgia"},{"issue":"Suppl 1","key":"1043_CR24","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1046\/j.1526-4610.2002.0420s1003.x","volume":"42","author":"RB Lipton","year":"2002","unstructured":"Lipton RB, Hamelsky SW, Dayno JM. What do patients with migraine want from acute migraine treatment? Headache. 2002;42(Suppl 1):3\u20139.","journal-title":"Headache"},{"issue":"Suppl 2","key":"1043_CR25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/j.1468-2982.2004.00893.x","volume":"24","author":"R Gallagher","year":"2004","unstructured":"Gallagher R. What do patients want from acute migraine treatment? Cephalalgia. 2004;24(Suppl 2):8\u201315.","journal-title":"Cephalalgia"},{"issue":"6","key":"1043_CR26","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1080\/00325481.2025.2518043","volume":"137","author":"SJ Tepper","year":"2025","unstructured":"Tepper SJ, Pavlovic JM, Yu S, et al. Efficacy and safety of rimegepant 75 mg for acute treatment of migraine: a pooled analysis of four randomized, placebo-controlled trials. Postgrad Med. 2025;137(6):503\u201313.","journal-title":"Postgrad Med"},{"key":"1043_CR27","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1\u2013211.","DOI":"10.1177\/0333102417738202"},{"key":"1043_CR28","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.2147\/JPR.S453806","volume":"17","author":"RB Lipton","year":"2024","unstructured":"Lipton RB, Thiry A, Morris BA, Croop R. Efficacy and safety of rimegepant 75 mg oral tablet, a CGRP receptor antagonist, for the acute treatment of migraine: a randomized, double-blind, placebo-controlled trial. J Pain Res. 2024;17:2431\u201341.","journal-title":"J Pain Res"},{"issue":"2","key":"1043_CR29","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1056\/NEJMoa1811090","volume":"381","author":"RB Lipton","year":"2019","unstructured":"Lipton RB, Croop R, Stock EG, et al. Rimegepant, an oral calcitonin gene-related peptide receptor antagonist, for migraine. N Engl J Med. 2019;381(2):142\u20139.","journal-title":"N Engl J Med"},{"issue":"10200","key":"1043_CR30","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/S0140-6736(19)31606-X","volume":"394","author":"R Croop","year":"2019","unstructured":"Croop R, Goadsby PJ, Stock DA, et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019;394(10200):737\u201345.","journal-title":"Lancet"},{"issue":"6","key":"1043_CR31","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/S1474-4422(23)00126-6","volume":"22","author":"S Yu","year":"2023","unstructured":"Yu S, Kim BK, Guo A, et al. Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2023;22(6):476\u201384.","journal-title":"Lancet Neurol"},{"issue":"1","key":"1043_CR32","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ncl.2025.08.011","volume":"44","author":"NRA Bruijn","year":"2026","unstructured":"Bruijn NRA, Huessler EM, MaassenVanDenBrink A, et al. Placebo response in acute and prophylactic treatment of migraine: a systematic review and meta-analysis covering 36 years of research. Neurol Clin. 2026;44(1):23\u201345.","journal-title":"Neurol Clin"},{"issue":"7","key":"1043_CR33","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1046\/j.1468-2982.2003.00528.x","volume":"23","author":"L Bendtsen","year":"2003","unstructured":"Bendtsen L, Mattsson P, Zwart JA, Lipton RB. Placebo response in clinical randomized trials of analgesics in migraine. Cephalalgia. 2003;23(7):487\u201390.","journal-title":"Cephalalgia"},{"issue":"5","key":"1043_CR34","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1111\/head.13511","volume":"59","author":"NA Hindiyeh","year":"2019","unstructured":"Hindiyeh NA, Kellerman DJ, Schmidt PC. Review of acute treatment of migraine trial results with the new FDA endpoints: design implications for future trials. Headache. 2019;59(5):819\u201324.","journal-title":"Headache"},{"issue":"6","key":"1043_CR35","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1177\/0333102419828967","volume":"39","author":"HC Diener","year":"2019","unstructured":"Diener HC, Tassorelli C, Dodick DW, et al. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: fourth edition. Cephalalgia. 2019;39(6):687\u2013710.","journal-title":"Cephalalgia"},{"issue":"1","key":"1043_CR36","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41572-022-00415-0","volume":"9","author":"S Ashina","year":"2023","unstructured":"Ashina S, Terwindt GM, Steiner TJ, et al. Medication overuse headache. Nat Rev Dis Primers. 2023;9(1):5.","journal-title":"Nat Rev Dis Primers"},{"issue":"10161","key":"1043_CR37","doi-asserted-by":"publisher","first-page":"2280","DOI":"10.1016\/S0140-6736(18)32534-0","volume":"392","author":"U Reuter","year":"2018","unstructured":"Reuter U, Goadsby PJ, Lanteri-Minet M, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392(10161):2280\u20137.","journal-title":"Lancet"},{"issue":"4","key":"1043_CR38","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/S1474-4422(24)00025-5","volume":"23","author":"C Tassorelli","year":"2024","unstructured":"Tassorelli C, Nagy K, Pozo-Rosich P, et al. Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial. Lancet Neurol. 2024;23(4):382\u201392.","journal-title":"Lancet Neurol"},{"issue":"10","key":"1043_CR39","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/S1474-4422(20)30279-9","volume":"19","author":"WM Mulleners","year":"2020","unstructured":"Mulleners WM, Kim BK, L\u00e1inez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2020;19(10):814\u201325.","journal-title":"Lancet Neurol"}],"container-title":["Neurology and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-026-01043-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40120-026-01043-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-026-01043-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:06:33Z","timestamp":1791950793000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40120-026-01043-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,3]]},"references-count":39,"alternative-id":["1043"],"URL":"https:\/\/doi.org\/10.1007\/s40120-026-01043-6","relation":{},"ISSN":["2193-8253","2193-6536"],"issn-type":[{"value":"2193-8253","type":"print"},{"value":"2193-6536","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,3]]},"assertion":[{"value":"9 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Michel Lanteri-Minet: Personal fees for consultancy activities from AbbVie\/Allergan, Amgen, Eli Lilly, IPSEN, Lundbeck, Novartis, Orion Pharma, Perfood, Pfizer, Reckitt-Benckiser, Teva, and UPSA. Timothy Smith: Personal fees for speakers bureau: AbbVie\/Allergan, Amgen, Biohaven, Lilly, and Novartis; advisory boards: AbbVie\/Allergan, Alder\/Lundbeck, Amgen, Biohaven, Impel Neuropharma, Lilly, Neurolief, Nocira, Nuvie, Teva, Theranica, and Vorso\/Nesos; research support: AbbVie\/Allergan, Aeon, Alder\/Lundbeck, Alnylam, Amgen, Biohaven, Boehringer Ingelheim, Charleston Labs, Electrocore, Graviton, Impel Neuropharma, Lilly, Merz Therapeutics, Nocira, Novartis, Novo Nordisk, Pfizer, Structure Therapeutics, Terns Pharmaceuticals, Teva, Theranica, and Vorso\/Nesos. Catherine Nalpas, Luz M Ramirez, Shannin McCollum, and Sara Ramaker: Employees of and hold stock\/options in Pfizer. Alexandra Thiry: Former employee of Biohaven Pharmaceuticals, owns stock in Biohaven Ltd, is an employee of Pfizer, and owns stock\/options in Pfizer. Robert Fountaine: Former employee of Pfizer (currently retired) and owns stock in Pfizer.","order":1,"name":"Ethics","label":"Conflicts of Interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by an institutional review board\/independent ethics committee for each participating site (Supplementary Table\u00a01). All participants provided written informed consent. The study was conducted in compliance with ethical principles of the Declaration of Helsinki and all International Council on Harmonization Good Clinical Practice Guidelines.","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}