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. 2018 Oct 29;18(1):118.
doi: 10.1186/s12874-018-0578-7.

Mediation analysis with a time-to-event outcome: a review of use and reporting in healthcare research

Lauren Lapointe-Shaw  1   2   3 , Zachary Bouck  4 , Nicholas A Howell  5   6   7 , Theis Lange  8   9 , Ani Orchanian-Cheff  10 , Peter C Austin  5   6 , Noah M Ivers  5   6   4   11 , Donald A Redelmeier  12   5   6 , Chaim M Bell  12   5   6   13
Affiliations

Mediation analysis with a time-to-event outcome: a review of use and reporting in healthcare research

Lauren Lapointe-Shaw et al. BMC Med Res Methodol. .

Abstract

Background: Mediation analysis tests whether the relationship between two variables is explained by a third intermediate variable. We sought to describe the usage and reporting of mediation analysis with time-to-event outcomes in published healthcare research.

Methods: A systematic search of Medline, Embase, and Web of Science was executed in December 2016 to identify applications of mediation analysis to healthcare research involving a clinically relevant time-to-event outcome. We summarized usage over time and reporting of important methodological characteristics.

Results: We included 149 primary studies, published from 1997 to 2016. Most studies were published after 2011 (n = 110, 74%), and the annual number of studies nearly doubled in the last year (from n = 21 to n = 40). A traditional approach (causal steps or change in coefficient) was most commonly taken (n = 87, 58%), and the majority of studies (n = 114, 77%) used a Cox Proportional Hazards regression for the outcome. Few studies (n = 52, 35%) mentioned any of the assumptions or limitations fundamental to a causal interpretation of mediation analysis.

Conclusion: There is increasing use of mediation analysis with time-to-event outcomes. Current usage is limited by reliance on traditional methods and the Cox Proportional Hazards model, as well as low rates of reporting of underlying assumptions. There is a need for formal criteria to aid authors, reviewers, and readers reporting or appraising such studies.

Keywords: Counterfactuals; Indirect effect; Mediation; Mediation analysis, Survival, Time-to-event, Methodology; Reporting.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

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Not applicable.

Competing interests

TL reports personal fees from Novo Nordisk and BeiGene, outside the submitted work. The remaining authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Causal diagram depicting the relationship between independent (x), dependent (y), and mediator (z) variables
Fig. 2
Fig. 2
An example of mediation analysis in healthcare research
Fig. 3
Fig. 3
PRISMA Flow Diagram
Fig. 4
Fig. 4
Included studies, by year of publication
Fig. 5
Fig. 5
Included studies by year, according to their approach to mediation analysis
See this image and copyright information in PMC

References

    1. MacKinnon DP, Fairchild AJ, Fritz MS. Mediation analysis. Annu Rev Psychol. 2007;58:593–614. doi: 10.1146/annurev.psych.58.110405.085542. - DOI - PMC - PubMed
    1. Valeri L, Vanderweele TJ. Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros.[Erratum appears in Psychol Methods. 2013 Dec;18(4):474] Psychol Methods. 2013;18(2):137–150. doi: 10.1037/a0031034. - DOI - PMC - PubMed
    1. Lange T, Rasmussen M, Thygesen LC. Assessing natural direct and indirect effects through multiple pathways. Am J Epidemiol. 2014;179(4):513–518. doi: 10.1093/aje/kwt270. - DOI - PubMed
    1. Fairchild AJ, MacKinnon DP. A general model for testing mediation and moderation effects. Prev Sci. 2009;10(2):87–99. doi: 10.1007/s11121-008-0109-6. - DOI - PMC - PubMed
    1. Preacher KJ, Rucker DD, Hayes AF. Addressing moderated mediation hypotheses: theory, methods, and prescriptions. Multivar Behav Res. 2007;42(1):185–227. doi: 10.1080/00273170701341316. - DOI - PubMed

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