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Indirect effects in mediation analyses should not be tested for statistical significance
1Department of Epidemiology and Data Science, University Medical Centres, Amsterdam, The Netherlands.
Mediation analysis reveals issues with indirect effect standard errors, particularly when exposure-mediator and mediator-outcome relationships are equally strong. Clinical relevance, not statistical significance, should guide the evaluation of indirect effects.
Area of Science:
- Epidemiology
- Biostatistics
Background:
- Mediation analysis dissects exposure-outcome effects into direct and indirect components.
- A common issue in mediation analysis is the underestimation of the indirect effect's standard error compared to direct and total effects.
- This standard error problem is often overlooked in epidemiological research.
Purpose of the Study:
- To highlight the problem of standard error estimation for indirect effects in mediation analysis.
- To offer guidance on statistically testing indirect effects.
Main Methods:
- Utilized two real-world datasets for illustration.
- Conducted several simulations to investigate the standard error estimation problem.
Main Results:
- The standard error estimation issue is most significant when exposure-mediator and mediator-outcome relationships are of comparable strength.
- The magnitude of this estimation problem varies depending on the strength of the mediation effect.
Conclusions:
- Statistical significance testing for indirect effects in mediation analysis is discouraged.
- The clinical relevance of mediation should be the primary consideration for evaluation.
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