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EClinicalMedicine 1 (2018) 21–27 https://doi.org/10.1016/j.eclinm.2018.06.005 2589-5370/© 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). EClinicalMedicine: journal homepage: https://www.journals.elsevier.com/ eclinicalmedicine Research Paper