Prevention Science

, Volume 16, Issue 8, pp 1128–1135

Sample Size for Joint Testing of Indirect Effects


DOI: 10.1007/s11121-014-0528-5

Cite this article as:
Vittinghoff, E. & Neilands, T.B. Prev Sci (2015) 16: 1128. doi:10.1007/s11121-014-0528-5


This paper presents methods to calculate sample size for evaluating mediation by joint testing of both links in an indirect pathway from exposure to mediator to outcome. Calculations rely on simulations of the underlying data structure, with testing of the two links performed under the simplifying assumption that the two test statistics are asymptotically independent. Simulations show that the proposed methods are accurate. Continuous and binary exposures and mediators, as well as continuous, binary, count, and survival outcomes are accommodated, along with over-dispersion of count outcomes, design effects, and confounding of the exposure-mediator and mediator-outcome relationships. An illustrative example is provided, and a documented R program implementing the calculations is available online.


Mediation Indirect pathway Sample size Power Generalized linear models. 

Supplementary material

11121_2014_528_MOESM1_ESM.pdf (66 kb)
(PDF 65.9 KB)
11121_2014_528_MOESM2_ESM.txt (32 kb)
(TXT 31.9 KB)
11121_2014_528_MOESM3_ESM.pdf (184 kb)
(PDF 183 KB)

Copyright information

© Society for Prevention Research 2014

Authors and Affiliations

  1. 1.Department of Epidemiology and BiostatisticsUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Department of Medicine, Center for AIDS Prevention StudiesUniversity of California San FranciscoSan FranciscoUSA

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