European Journal of Epidemiology

, Volume 34, Issue 3, pp 225–233 | Cite as

The meaning of confounding adjustment in the presence of multiple versions of treatment: an application to organ transplantation

  • Kerollos Nashat WanisEmail author
  • Arin L. Madenci
  • Mary Katherine Dokus
  • Mark S. Orloff
  • Mark A. Levstik
  • Roberto Hernandez-Alejandro
  • Miguel A. Hernán


Causal inference for treatments with many versions requires a careful specification of the versions of treatment. Specifically, the existence of multiple relevant versions of treatment has implications for the selection of confounders. To illustrate this, we estimate the effect of organ transplantation using grafts from donors who died due to anoxic drug overdose, on recipient graft survival in the US. We describe how explicitly outlining the target trial (i.e. the hypothetical randomized trial which would answer the causal question of interest) to be emulated by an observational study analysis helps conceptualize treatment versions, guides selection of appropriate adjustment variables, and helps clarify the settings in which causal effects of compound treatments will be of value to decision-makers.


Compound treatments Treatment versions Transportability Generalizability Transplantation 



The data reported here have been supplied by the Hennepin Healthcare Research Institute (HHRI) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the US Government.

Supplementary material

10654_2019_484_MOESM1_ESM.docx (62 kb)
Supplementary material 1 (DOCX 61 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Surgery, London Health Sciences CentreWestern UniversityLondonCanada
  2. 2.Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  3. 3.Division of TransplantationUniversity of RochesterNew YorkUSA
  4. 4.Division of Transplantation/Hepatobiliary Surgery, Department of SurgeryUniversity of RochesterNew YorkUSA
  5. 5.Department of BiostatisticsHarvard T.H. Chan School of Public HealthBostonUSA
  6. 6.Harvard-MIT Division of Health Sciences and TechnologyCambridgeUSA

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