Automated causal inference in application to randomized controlled clinical trials

arXiv (Cornell University)

Abstract

Randomized controlled trials (RCTs) are considered as the gold standard for testing causal hypotheses in the clinical domain. However, the investigation of prognostic variables of patient outcome in a hypothesized cause-effect route is not feasible using standard statistical methods. Here, we propose a new automated causal inference method (AutoCI) built upon the invariant causal prediction (ICP) framework for the causal re-interpretation of clinical trial data. Compared to existing methods, we show that the proposed AutoCI allows to efficiently determine the causal variables with a clear differentiation on two real-world RCTs of endometrial cancer patients with mature outcome and extensive clinicopathological and molecular data. This is achieved via suppressing the causal probability of non-causal variables by a wide margin. In ablation studies, we further demonstrate that the assignment of causal probabilities by AutoCI remain consistent in the presence of confounders. In conclusion, these results confirm the robustness and feasibility of AutoCI for future applications in real-world clinical analysis.

Authors 13

1. Jiqing Wu
2. Nanda Horeweg Aachen Department of Radiation Oncology

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiation Oncology , Leiden University Medical Center , Leiden , The Netherlands

3. Marco de Bruyn

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Obstetrics and Gynecology , University of Groningen , University Medical Center Groningen , Groningen , The Netherlands

4. Remi A. Nout Aachen Department of Radiation Oncology

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiation Oncology , Leiden University Medical Center , Leiden , The Netherlands

5. Ina Maria Jurgenliemk-Schulz
6. Ludy C.H.W. Lutgens

   Maastricht University Medical Centre · Maastro Clinic

   Affiliation as printed

   Maastricht Radiation Oncology Clinic , Maastricht , The Netherlands

7. Jan J. Jobsen

   Medisch Spectrum Twente

   Affiliation as printed

   Department of Radiotherapy , Medisch Spectrum Twente , Enschede , The Netherlands

8. Elzbieta M. van der Steen‐Banasik

   Radiotherapiegroep

   Affiliation as printed

   Radiotherapiegroep , Arnhem , The Netherlands

9. Hans W. Nijman

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Obstetrics and Gynecology , University of Groningen , University Medical Center Groningen , Groningen , The Netherlands

10. Vincent T.H.B.M. Smit Aachen Department of Pathology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Pathology , Leiden University Medical Center , Leiden , The Netherlands

11. Tjalling Bosse Aachen Department of Pathology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Pathology , Leiden University Medical Center , Leiden , The Netherlands

12. Carien L. Creutzberg Aachen Department of Radiation Oncology

    Leiden University Medical Center

    Affiliation as printed

    Department of Radiation Oncology , Leiden University Medical Center , Leiden , The Netherlands

13. Viktor Hendrik Koelzer