Morris, Tim P;
Walker, A Sarah;
Williamson, Elizabeth J;
White, Ian R;
(2022)
Planning a method for covariate adjustment in individually randomised trials: a practical guide.
Trials
, 23
, Article 328. 10.1186/s13063-022-06097-z.
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Abstract
Background: It has long been advised to account for baseline covariates in the analysis of confirmatory randomised trials, with the main statistical justifications being that this increases power and, when a randomisation scheme balanced covariates, permits a valid estimate of experimental error. There are various methods available to account for covariates but it is not clear how to choose among them. // Methods: Taking the perspective of writing a statistical analysis plan, we consider how to choose between the three most promising broad approaches: direct adjustment, standardisation and inverse-probability-of-treatment weighting. // Results: The three approaches are similar in being asymptotically efficient, in losing efficiency with mis-specified covariate functions and in handling designed balance. If a marginal estimand is targeted (for example, a risk difference or survival difference), then direct adjustment should be avoided because it involves fitting non-standard models that are subject to convergence issues. Convergence is most likely with IPTW. Robust standard errors used by IPTW are anti-conservative at small sample sizes. All approaches can use similar methods to handle missing covariate data. With missing outcome data, each method has its own way to estimate a treatment effect in the all-randomised population. We illustrate some issues in a reanalysis of GetTested, a randomised trial designed to assess the effectiveness of an electonic sexually transmitted infection testing and results service. // Conclusions: No single approach is always best: the choice will depend on the trial context. We encourage trialists to consider all three methods more routinely.
| Type: | Article |
|---|---|
| Title: | Planning a method for covariate adjustment in individually randomised trials: a practical guide |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13063-022-06097-z |
| Publisher version: | https://doi.org/10.1186/s13063-022-06097-z |
| Language: | English |
| Additional information: | 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. |
| Keywords: | Covariate adjustment; Estimands; Standardisation; Inverse probability of treatment weighting; Randomised controlled trials; Clinical trials; Missing data |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10146925 |
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