Treatment estimands in clinical trials of patients hospitalised for COVID-19: Ensuring trials ask the right questions

dc.contributor.authorKahan, Brennan C.
dc.contributor.authorMorris, Tim P.
dc.contributor.authorWhite, Ian R.
dc.contributor.authorTweed, Conor D.
dc.contributor.authorCro, Suzie
dc.contributor.authorDahly, Darren
dc.contributor.authorPham, Tra My
dc.contributor.authorEsmail, Hanif
dc.contributor.authorBabiker, Abdel
dc.contributor.authorCarpenter, James R.
dc.contributor.funderMedical Research Councilen
dc.description.abstractWhen designing a clinical trial, explicitly defining the treatment estimands of interest (that which is to be estimated) can help to clarify trial objectives and ensure the questions being addressed by the trial are clinically meaningful. There are several challenges when defining estimands. Here, we discuss a number of these in the context of trials of treatments for patients hospitalised with COVID-19 and make suggestions for how estimands should be defined for key outcomes. We suggest that treatment effects should usually be measured as differences in proportions (or risk or odds ratios) for outcomes such as death and requirement for ventilation, and differences in means for outcomes such as the number of days ventilated. We further recommend that truncation due to death should be handled differently depending on whether a patient- or resource-focused perspective is taken; for the former, a composite approach should be used, while for the latter, a while-alive approach is preferred. Finally, we suggest that discontinuation of randomised treatment should be handled from a treatment policy perspective, where non-adherence is ignored in the analysis (i.e. intention to treat).en
dc.description.sponsorshipMedical Research Council (MC_UU_12023/21; MC_UU_12023/29)
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.identifier.citationKahan, B. C., Morris, T. P., White, I. R., Tweed, C. D., Cro, S., Dahly, D., Pham, T. M., Esmail, H., Babiker, A. and Carpenter, J. R. (2020) ‘Treatment estimands in clinical trials of patients hospitalised for COVID-19: ensuring trials ask the right questions’, BMC Medicine, 18(1), 286 (8pp). doi: 10.1186/s12916-020-01737-0en
dc.identifier.journaltitleBMC Medicineen
dc.publisherBioMed Central Ltden
dc.rights© 2020, the Authors. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.en
dc.subjectIntercurrent eventsen
dc.subjectRandomised trialen
dc.titleTreatment estimands in clinical trials of patients hospitalised for COVID-19: Ensuring trials ask the right questionsen
dc.typeArticle (peer-reviewed)en
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