Abstract
Purpose
Propensity trimming, hierarchical modelling and instrumental variable (IV) analysis are statistical techniques dealing with confounding, cluster-related variation or confounding by severity. This study aimed to explain (dis)advantages of these techniques in estimating the effect of breast-conserving therapy (BCT) and mastectomy on 10-year distant metastasis-free survival (DMFS).
Methods
All women diagnosed in 2005 with primary T1-2N0-1 breast cancer treated with BCT or mastectomy were selected from the Netherlands Cancer Registry. We used multivariable Cox regression to correct for confounding. Propensity trimming was used to create a more homogeneous population for which the treatment choice was not self-evident. Hospital of surgery was used as hierarchical level to handle hospital-related variation, and as IV to deal with unmeasured confounding.
Results
Multivariable Cox regression showed higher 10-year DMFS for BCT than mastectomy [HR 0.70 (95% CI 0.60–82)]. Propensity trimming on the 10–90th and the 20–80th percentile of the propensity score distribution and hierarchical modelling showed similar HRs. IV analysis showed no significant difference between BCT and mastectomy.
Conclusion
Unmeasured confounding is very difficult to eliminate in observational research. We cannot conclude that BCT or mastectomy has a causal relationship with 10-year DMFS. It is crucial to critically evaluate all model’s assumptions, and to be careful in drawing firm conclusions.
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Acknowledgements
The authors thank the registration team of the Netherlands Comprehensive Cancer Organisation (IKNL) for the collection of data for the Netherlands Cancer Registry.
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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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van Maaren, M.C., le Cessie, S., Strobbe, L.J.A. et al. Different statistical techniques dealing with confounding in observational research: measuring the effect of breast-conserving therapy and mastectomy on survival. J Cancer Res Clin Oncol 145, 1485–1493 (2019). https://doi.org/10.1007/s00432-019-02919-x
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DOI: https://doi.org/10.1007/s00432-019-02919-x