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For large observational studies lacking a control group (unlike randomized controlled trials, RCT), propensity scores (PS) are often the method of choice to account for pre-treatment confounding in baseline characteristics, and thereby avoid substantial bias in treatment estimation. A vast majority of PS techniques focus on average treatment effect estimation, without any clear consensus on how to account for confounders, especially in a multiple treatment setting. Furthermore, for time-to event outcomes, the analytical framework is further complicated in presence of high censoring rates (sometimes, due to non-susceptibility of study units to a disease), imbalance between treatment groups, and clustered nature of the data (where, survival outcomes appear in groups). Motivated by a right-censored kidney transplantation dataset derived from the United Network of Organ Sharing (UNOS), we investigate and compare two recent promising PS procedures, (a) the generalized boosted model (GBM), and (b) the covariate-balancing propensity score (CBPS), in an attempt to decouple the causal effects of treatments (here, study subgroups, such as hepatitis C virus (HCV) positive/negative donors, and positive/negative recipients) on time to death of kidney recipients due to kidney failure, post transplantation. For estimation, we employ a 2-step procedure which addresses various complexities observed in the UNOS database within a unified paradigm. First, to adjust for the large number of confounders on the multiple sub-groups, we fit multinomial PS models via procedures (a) and (b). In the next stage, the estimated PS is incorporated into the likelihood of a semi-parametric cure rate Cox proportional hazard frailty model via inverse probability of treatment weighting, adjusted for multi-center clustering and excess censoring, Our data analysis reveals a more informative and superior performance of the full model in terms of treatment effect estimation, over sub-models that relaxes the various features of the event time dataset.
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Depth importance in precision medicine (DIPM): a tree- and forest-based method for right-censored survival outcomes
Summary Many clinical trials have been conducted to compare right-censored survival outcomes between interventions. Such comparisons are typically made on the basis of the entire group receiving one intervention versus the others. In order to identify subgroups for which the preferential treatment may differ from the overall group, we propose the depth importance in precision medicine (DIPM) method for such data within the precision medicine framework. The approach first modifies the split criteria of the traditional classification tree to fit the precision medicine setting. Then, a random forest of trees is constructed at each node. The forest is used to calculate depth variable importance scores for each candidate split variable. The variable with the highest score is identified as the best variable to split the node. The importance score is a flexible and simply constructed measure that makes use of the observation that more important variables tend to be selected closer to the root nodes of trees. The DIPM method is primarily designed for the analysis of clinical data with two treatment groups. We also present the extension to the case of more than two treatment groups. We use simulation studies to demonstrate the accuracy of our method and provide the results of applications to two real-world data sets. In the case of one data set, the DIPM method outperforms an existing method, and a primary motivation of this article is the ability of the DIPM method to address the shortcomings of this existing method. Altogether, the DIPM method yields promising results that demonstrate its capacity to guide personalized treatment decisions in cases with right-censored survival outcomes.
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- Award ID(s):
- 1722544
- PAR ID:
- 10169022
- Date Published:
- Journal Name:
- Biostatistics
- ISSN:
- 1465-4644
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/biostatistics/kxaa021
