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. 2017 Jun 13;17:90. doi: 10.1186/s12874-017-0364-y

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© The Author(s) 2017

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Fig. 1 — Structure of the simulation. On the left side the determination of reference values is illustrated and on the right side the structure of the simulation procedure. *This step is skipped for the first part of simulation where the best simulation model was investigated and only used to determine the needed sample size of a pilot study