Search for: All records

The widespread use of machine learning algorithms in radiomics has led to a proliferation of flexible prognostic models for clinical outcomes. However, a limitation of these techniques is their black-box nature, which prevents the ability for increased mechanistic phenomenological understanding. In this article, we develop an inferential framework for estimating causal effects with radiomics data. A new challenge is that the exposure of interest is latent so that new estimation procedures are needed. We leverage a multivariate version of partial least squares for causal effect estimation. The methodology is illustrated with applications to two radiomics datasets, one in osteosarcoma and one in glioblastoma. 

Abstract Background Evidence to guide type 2 diabetes treatment individualization is limited. We evaluated heterogeneous treatment effects (HTE) of intensive glycemic control in type 2 diabetes patients on major adverse cardiovascular events (MACE) in the Action to Control Cardiovascular Risk in Diabetes Study (ACCORD) and the Veterans Affairs Diabetes Trial (VADT). Methods Causal forests machine learning analysis was performed using pooled individual data from two randomized trials (n = 12,042) to identify HTE of intensive versus standard glycemic control on MACE in patients with type 2 diabetes. We used variable prioritization from causal forests to build a summary decision tree and examined the risk difference of MACE between treatment arms in the resulting subgroups. Results A summary decision tree used five variables (hemoglobin glycation index, estimated glomerular filtration rate, fasting glucose, age, and body mass index) to define eight subgroups in which risk differences of MACE ranged from − 5.1% (95% CI − 8.7, − 1.5) to 3.1% (95% CI 0.2, 6.0) (negative values represent lower MACE associated with intensive glycemic control). Intensive glycemic control was associated with lower MACE in pooled study data in subgroups with low (− 4.2% [95% CI − 8.1, − 1.0]), intermediate (− 5.1% [95% CI − 8.7, − 1.5]), and high (− 4.3% [95% CI − 7.7, − 1.0]) MACE rates with consistent directions of effect in ACCORD and VADT alone. Conclusions This data-driven analysis provides evidence supporting the diabetes treatment guideline recommendation of intensive glucose lowering in diabetes patients with low cardiovascular risk and additionally suggests potential benefits of intensive glycemic control in some individuals at higher cardiovascular risk. 

In many medical and scientific settings, the choice of treatment or intervention may be de-termined by a covariate threshold. For example, elderly men may receive more thoroughdiagnosis if their prostate-specific antigen (PSA) level is high. In these cases, the causaltreatment effect is often of great interest, especially when there is a lack of evidence fromrandomized clinical trials. From the social science literature, a class of methods known asregression discontinuity (RD) designs can be used to estimate the treatment effect in thissituation. Under certain assumptions, such an estimand enjoys a causal interpretation. Weshow how to estimate causal effects under the regression discontinuity design for censoreddata. The proposed estimation procedure employs a class of censoring unbiased transfor-mations that includes inverse probability censored weighting and doubly robust transfor-mation schemes. Simulation studies are used to evaluate the finite-sample properties of theproposed estimator. We also illustrate the proposed method by evaluating the causal effectof PSA-dependent screening strategies 

A common goal in observational research is to estimate marginal causal effects in the presence of confounding variables. One solution to this problem is to use the covariate distribution to weight the outcomes such that the data appear randomized. The propensity score is a natural quantity that arises in this setting. Propensity score weights have desirable asymptotic properties, but they often fail to adequately balance covariate data in finite samples. Empirical covariate balancing methods pose as an appealing alternative by exactly balancing the sample moments of the covariate distribution. With this objective in mind, we propose a framework for estimating balancing weights by solving a constrained convex program, where the criterion function to be optimized is a Bregman distance. We then show that the different distances in this class render identical weights to those of other covariate balancing methods. A series of numerical studies are presented to demonstrate these similarities. 

A powerful tool for the analysis of nonrandomized observational studies has been the potential outcomes model. Utilization of this framework allows analysts to estimate average treatment effects. This article considers the situation in which high-dimensional covariates are present and revisits the standard assumptions made in causal inference. We show that by employing a flexible Gaussian process framework, the assumption of strict overlap leads to very restrictive assumptions about the distribution of covariates, results for which can be characterized using classical results from Gaussian random measures as well as reproducing kernel Hilbert space theory. In addition, we propose a strategy for data-adaptive causal effect estimation that does not rely on the strict overlap assumption. These findings reveal under a focused framework the stringency that accompanies the use of the treatment positivity assumption in high-dimensional settings. 

We show how entropy balancing can be used for transporting experimental treatment effects from a trial population onto a target population. This method is doubly robust in the sense that if either the outcome model or the probability of trial participation is correctly specified, then the estimate of the target population average treatment effect is consistent. Furthermore, we only require the sample moments of the effect modifiers drawn from the target population to consistently estimate the target population average treatment effect. We compared the finite‐sample performance of entropy balancing with several alternative methods for transporting treatment effects between populations. Entropy balancing techniques are efficient and robust to violations of model misspecification. We also examine the results of our proposed method in an applied analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial transported to a sample of US adults with diabetes taken from the National Health and Nutrition Examination Survey cohort.