Causal inference in survival analysis using pseudo-observations

Stat Med. 2017 Jul 30;36(17):2669-2681. doi: 10.1002/sim.7297. Epub 2017 Apr 6.

Abstract

Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs to address right-censoring, and often, special techniques are required for that purpose. We will show how censoring can be dealt with 'once and for all' by means of so-called pseudo-observations when doing causal inference in survival analysis. The pseudo-observations can be used as a replacement of the outcomes without censoring when applying 'standard' causal inference methods, such as (1) or (2) earlier. We study this idea for estimating the average causal effect of a binary treatment on the survival probability, the restricted mean lifetime, and the cumulative incidence in a competing risks situation. The methods will be illustrated in a small simulation study and via a study of patients with acute myeloid leukemia who received either myeloablative or non-myeloablative conditioning before allogeneic hematopoetic cell transplantation. We will estimate the average causal effect of the conditioning regime on outcomes such as the 3-year overall survival probability and the 3-year risk of chronic graft-versus-host disease. Copyright © 2017 John Wiley & Sons, Ltd.

Keywords: G-formula; causal inference; propensity score; pseudo-observations; right-censoring; survival data.

MeSH terms

  • Bias*
  • Causality*
  • Computer Simulation
  • Confounding Factors, Epidemiologic
  • Data Interpretation, Statistical
  • Female
  • Graft vs Host Disease
  • Humans
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Monte Carlo Method
  • Myeloablative Agonists
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic / methods*
  • Survival Analysis*
  • Treatment Outcome

Substances

  • Myeloablative Agonists