Candlish, J. orcid.org/0000-0001-5280-7891, Pate, A., Sperrin, M. et al. (1 more author) (2017) Evaluation of biases present in the cohort multiple randomised controlled trial design: a simulation study. BMC Medical Research Methodology, 17 (17).
Abstract
Background The cohort multiple randomised controlled trial (cmRCT) design provides an opportunity to incorporate the benefits of randomisation within clinical practice; thus reducing costs, integrating electronic healthcare records, and improving external validity. This study aims to address a key concern of the cmRCT design: refusal to treatment is only present in the intervention arm, and this may lead to bias and reduce statistical power.
Methods We used simulation studies to assess the effect of this refusal, both random and related to event risk, on bias of the effect estimator and statistical power. A series of simulations were undertaken that represent a cmRCT trial with time-to-event endpoint. Intention-to-treat (ITT), per protocol (PP), and instrumental variable (IV) analysis methods, two stage predictor substitution and two stage residual inclusion, were compared for various refusal scenarios.
Results We found the IV methods provide a less biased estimator for the causal effect when refusal is present in the intervention arm, with the two stage residual inclusion method performing best with regards to minimum bias and sufficient power. We demonstrate that sample sizes should be adapted based on expected and actual refusal rates in order to be sufficiently powered for IV analysis.
Conclusion We recommend running both an IV and ITT analyses in an individually randomised cmRCT as it is expected that the effect size of interest, or the effect we would observe in clinical practice, would lie somewhere between that estimated with ITT and IV analyses. The optimum (in terms of bias and power) instrumental variable method was the two stage residual inclusion method. We recommend using adaptive power calculations, updating them as refusal rates are collected in the trial recruitment phase in order to be sufficiently powered for IV analysis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s). 2017. 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. |
Keywords: | Trials within cohorts; Cohort multiple randomised controlled trial; Pragmatic trial; Instrumental variable |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Jul 2017 14:02 |
Last Modified: | 09 Oct 2019 14:54 |
Published Version: | https://doi.org/10.1186/s12874-017-0295-7 |
Status: | Published |
Publisher: | BioMed Central |
Refereed: | Yes |
Identification Number: | 10.1186/s12874-017-0295-7 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:118058 |