Landau, Sabine, Emsley, Richard, Dunn, Graham · Clinical trials (London, England) · 2018 · DOI
This study explains the best way to analyze how a treatment works by breaking down its effects into direct and indirect pathways. The researchers tested different statistical methods using a rehabilitation trial in ME/CFS patients and found that one approach (called analysis of covariance) gives the most reliable answers by measuring patients' symptoms before and after treatment.
This study is important because understanding *how* rehabilitation and other treatments work in ME/CFS—through which mechanisms they produce benefit—requires rigorous mediation analysis. The recommendation to always measure baseline mediators and use appropriate statistical methods ensures that future trials can reliably identify which aspects of treatment truly drive clinical improvement, informing more targeted therapeutic development.
This is a methodological study, not a clinical trial; it does not prove that rehabilitation is effective for ME/CFS or establish the true magnitude of any mediation effect. The findings apply only to continuous outcomes; categorical or time-to-event mediators may require different approaches. The causal conclusions rest on the assumption that the data generating model used in simulations accurately reflects real confounding structures.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Landau, Sabine, Emsley, Richard, & Dunn, Graham (2018). Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.. Clinical trials (London, England). https://doi.org/10.1177/1740774518760300
BibTeX
@article{mecfsatlas-landau-2018-beyond-total,
author = {Landau, Sabine and Emsley, Richard and Dunn, Graham},
title = {Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.},
journal = {Clinical trials (London, England)},
year = {2018},
doi = {10.1177/1740774518760300},
note = {PubMed: 29552919},
url = {https://www.mecfsatlas.com/evidence/landau-2018-beyond-total},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/landau-2018-beyond-total
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