Pate, A., Candlish, J. orcid.org/0000-0001-5280-7891, Sperrin, M. et al. (1 more author) (2016) Cohort Multiple Randomised Controlled Trials (cmRCT) design: efficient but biased? A simulation study to evaluate the feasibility of the Cluster cmRCT design. BMC Medical Research Methodology, 16 (109).
Abstract
Background The Cohort Multiple Randomised Controlled Trial (cmRCT) is a newly proposed pragmatic trial design; recently several cmRCT have been initiated. This study tests the unresolved question of whether differential refusal in the intervention arm leads to bias or loss of statistical power and how to deal with this.
Methods We conduct simulations evaluating a hypothetical cluster cmRCT in patients at risk of cardiovascular disease (CVD). To deal with refusal, we compare the analysis methods intention to treat (ITT), per protocol (PP) and two instrumental variable (IV) methods: two stage predictor substitution (2SPS) and two stage residual inclusion (2SRI) with respect to their bias and power. We vary the correlation between treatment refusal probability and the probability of experiencing the outcome to create different scenarios.
Results We found ITT to be biased in all scenarios, PP the most biased when correlation is strong and 2SRI the least biased on average. Trials suffer a drop in power unless the refusal rate is factored into the power calculation.
Conclusions The ITT effect in routine practice is likely to lie somewhere between the ITT and IV estimates from the trial which differ significantly depending on refusal rates. More research is needed on how refusal rates of experimental interventions correlate with refusal rates in routine practice to help answer the question of which analysis more relevant. We also recommend updating the required sample size during the trial as more information about the refusal rate is gained.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The Author(s). 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. |
Keywords: | Trials within Cohorts; Cohort multiple randomised controlled trial; Cluster; Pragmatic; 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: | 05 Jul 2017 08:54 |
Last Modified: | 05 Jul 2017 08:54 |
Published Version: | https://doi.org/10.1186/s12874-016-0208-1 |
Status: | Published |
Publisher: | BioMed Central |
Refereed: | Yes |
Identification Number: | 10.1186/s12874-016-0208-1 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:118059 |