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Stat Med. 2020 Feb 20;39(4):353-368. doi: 10.1002/sim.8407. Epub 2019 Nov 27.

Identification of the optimal treatment regimen in the presence of missing covariates.

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Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Biostatistics, Peking University, Beijing, China.


Covariates associated with treatment-effect heterogeneity can potentially be used to make personalized treatment recommendations towards best clinical outcomes. Methods for treatment-selection rule development that directly maximize treatment-selection benefits have attracted much interest in recent years, due to the robustness of these methods to outcome modeling. In practice, the task of treatment-selection rule development can be further complicated by missingness in data. Here, we consider the identification of optimal treatment-selection rules for a binary disease outcome when measurements of an important covariate from study participants are partly missing. Under the missing at random assumption, we develop a robust estimator of treatment-selection rules under the direct-optimization paradigm. This estimator targets the maximum selection benefits to the population under correct specification of at least one mechanism from each of the two sets-missing data or conditional covariate distribution, and treatment assignment or disease outcome model. We evaluate and compare performance of the proposed estimator with alternative direct-optimization estimators through extensive simulation studies. We demonstrate the application of the proposed method through a real data example from an Alzheimer's disease study for developing covariate combinations to guide the treatment of Alzheimer's disease.


augmented inverse probability weighting; biomarker; missing at random; robust; treatment-selection

[Available on 2021-02-20]

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