Estimating and testing sequential causal effects based on alternative G-formula: an observational study of the influence of early diagnosis on survival of cardia cancer

Abstract

Cancer diagnosis is part of a complex stochastic process, in which patients' personal and social characteristics influence the choice of diagnosing methods, diagnosing methods in turn influence the initial assessment of cancer stage, cancer stage in turn influences the choice of treating methods, and treating methods in turn influence cancer outcomes such as cancer survival. To evaluate the performance of diagnoses, one needs to estimate and test the sequential causal effect (SCE) under a specified regime of diagnoses and treatments in such a complex observational study, where the data-generating mechanism is unknown and modeling is needed for statistical inference. In this article, we introduce a method of statistical modeling to estimate and test SCEs under regimes of treatments (diagnoses and treatments in cancer diagnosis) in complex observational studies. By applying the alternative G-formula, we express the SCE in terms of the point effects of treatments in the sequence, so that the modeling can be conducted via the point effects in the framework of single-point causal inference. We illustrate our method by a medical example of cancer diagnosis with data from a Swedish prognosis study of cardia cancer.

KEYWORDS:

• Cancer diagnosis
• G-formula
• Point effect
• Sequential causal effect
• Statistical modeling

Ethics approval

The proposed research is covered by the ethical committee approval (DNR880113/13, §121) from the ethical review board of Uppsala University.

This work was supported by Vetenskapsrådet, Sweden (2019-02913).

Supplemental material

1. Data and code available in [Zenodo], at https://doi.org/10.5281/zenodo.6367502

2. A description of available methods (ii), (iii) and (iv) in the context of the medical example.

Additional information

Funding

This work is partially supported by the Swedish Research Council with the grant number 2019-02913.