arXiv subjects

Arman Sabbaghi

Publications and source records attributed to Arman Sabbaghi.

9 recordsLinked to original sources

arXiv2025

Degree of Interference: A General Framework For Causal Inference Under Interference

One core assumption typically adopted for valid causal inference is that of no interference between experimental units, i.e., the outcome of an experimental unit is unaffected by the treatments assigned to other experimental units. This assumption can be violated in real-life experiments, which significantly complicates the task of causal inference. As the number of potential outcomes increases, it becomes challenging to disentangle direct treatment effects from ``spillover'' effects. Current methodologies are lacking, as they cannot handle arbitrary, unknown interference structures to permit inference on causal estimands. We present a general framework to address the limitations of existing approaches. Our framework is based on the new concept of the ``degree of interference'' (DoI). The DoI is a unit-level latent variable that captures the latent structure of interference. We also develop a data augmentation algorithm that adopts a blocked Gibbs sampler and Bayesian nonparametric methodology to perform inferences on the estimands under our framework. We illustrate the DoI concept and properties of our Bayesian methodology via extensive simulation studies and an analysis of a randomized experiment investigating the impact of a cash transfer program for which interference is a critical concern. Ultimately, our framework enables us to infer causal effects without strong structural assumptions on interference.

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arXiv2024

Enhancing Longitudinal Clinical Trial Efficiency with Digital Twins and Prognostic Covariate-Adjusted Mixed Models for Repeated Measures (PROCOVA-MMRM)

Clinical trials are critical in advancing medical treatments but often suffer from immense time and financial burden. Advances in statistical methodologies and artificial intelligence (AI) present opportunities to address these inefficiencies. Here we introduce Prognostic Covariate-Adjusted Mixed Models for Repeated Measures (PROCOVA-MMRM) as an advantageous combination of prognostic covariate adjustment (PROCOVA) and Mixed Models for Repeated Measures (MMRM). PROCOVA-MMRM utilizes time-matched prognostic scores generated from AI models to enhance the precision of treatment effect estimators for longitudinal continuous outcomes, enabling reductions in sample size and enrollment times. We first provide a description of the background and implementation of PROCOVA-MMRM, followed by two case study reanalyses where we compare the performance of PROCOVA-MMRM versus the unadjusted MMRM. These reanalyses demonstrate significant improvements in statistical power and precision in clinical indications with unmet medical need, specifically Alzheimer's Disease (AD) and Amyotrophic Lateral Sclerosis (ALS). We also explore the potential for sample size reduction with the prospective implementation of PROCOVA-MMRM, finding that the same or better results could have been achieved with fewer participants in these historical trials if the enhanced precision provided by PROCOVA-MMRM had been prospectively leveraged. We also confirm the robustness of the statistical properties of PROCOVA-MMRM in a variety of realistic simulation scenarios. Altogether, PROCOVA-MMRM represents a rigorous method of incorporating advances in the prediction of time-matched prognostic scores generated by AI into longitudinal analysis, potentially reducing both the cost and time required to bring new treatments to patients while adhering to regulatory standards.

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arXiv2024

Prognostic Covariate Adjustment for Logistic Regression in Randomized Controlled Trials

Randomized controlled trials (RCTs) with binary primary endpoints introduce novel challenges for inferring the causal effects of treatments. The most significant challenge is non-collapsibility, in which the conditional odds ratio estimand under covariate adjustment differs from the unconditional estimand in the logistic regression analysis of RCT data. This issue gives rise to apparent paradoxes, such as the variance of the estimator for the conditional odds ratio from a covariate-adjusted model being greater than the variance of the estimator from the unadjusted model. We address this challenge in the context of adjustment based on predictions of control outcomes from generative artificial intelligence (AI) algorithms, which are referred to as prognostic scores. We demonstrate that prognostic score adjustment in logistic regression increases the power of the Wald test for the conditional odds ratio under a fixed sample size, or alternatively reduces the necessary sample size to achieve a desired power, compared to the unadjusted analysis. We derive formulae for prospective calculations of the power gain and sample size reduction that can result from adjustment for the prognostic score. Furthermore, we utilize g-computation to expand the scope of prognostic score adjustment to inferences on the marginal risk difference, relative risk, and odds ratio estimands. We demonstrate the validity of our formulae via extensive simulation studies that encompass different types of logistic regression model specifications. Our simulation studies also indicate how prognostic score adjustment can reduce the variance of g-computation estimators for the marginal estimands while maintaining frequentist properties such as asymptotic unbiasedness and Type I error rate control. Our methodology can ultimately enable more definitive and conclusive analyses for RCTs with binary primary endpoints.

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arXiv2024

Bayesian Prognostic Covariate Adjustment With Additive Mixture Priors

Effective and rapid decision-making from randomized controlled trials (RCTs) requires unbiased and precise treatment effect inferences. Two strategies to address this requirement are to adjust for covariates that are highly correlated with the outcome, and to leverage historical control information via Bayes' theorem. We propose a new Bayesian prognostic covariate adjustment methodology, referred to as Bayesian PROCOVA, that combines these two strategies. Covariate adjustment in Bayesian PROCOVA is based on generative artificial intelligence (AI) algorithms that construct a digital twin generator (DTG) for RCT participants. The DTG is trained on historical control data and yields a digital twin (DT) probability distribution for each RCT participant's outcome under the control treatment. The expectation of the DT distribution, referred to as the prognostic score, defines the covariate for adjustment. Historical control information is leveraged via an additive mixture prior with two components: an informative prior probability distribution specified based on historical control data, and a weakly informative prior distribution. The mixture weight determines the extent to which posterior inferences are drawn from the informative component, versus the weakly informative component. This weight has a prior distribution as well, and so the entire additive mixture prior is completely pre-specifiable without involving any RCT information. We establish an efficient Gibbs algorithm for sampling from the posterior distribution, and derive closed-form expressions for the posterior mean and variance of the treatment effect parameter conditional on the weight, in Bayesian PROCOVA. We evaluate efficiency gains of Bayesian PROCOVA via its bias control and variance reduction compared to frequentist PROCOVA in simulation studies that encompass different discrepancies. These gains translate to smaller RCTs.

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arXiv2023

A Weighted Prognostic Covariate Adjustment Method for Efficient and Powerful Treatment Effect Inferences in Randomized Controlled Trials

A crucial task for a randomized controlled trial (RCT) is to specify a statistical method that can yield an efficient estimator and powerful test for the treatment effect. A novel and effective strategy to obtain efficient and powerful treatment effect inferences is to incorporate predictions from generative artificial intelligence (AI) algorithms into covariate adjustment for the regression analysis of a RCT. Training a generative AI algorithm on historical control data enables one to construct a digital twin generator (DTG) for RCT participants, which utilizes a participant's baseline covariates to generate a probability distribution for their potential control outcome. Summaries of the probability distribution from the DTG are highly predictive of the trial outcome, and adjusting for these features via regression can thus improve the quality of treatment effect inferences, while satisfying regulatory guidelines on statistical analyses, for a RCT. However, a critical assumption in this strategy is homoskedasticity, or constant variance of the outcome conditional on the covariates. In the case of heteroskedasticity, existing covariate adjustment methods yield inefficient estimators and underpowered tests. We propose to address heteroskedasticity via a weighted prognostic covariate adjustment methodology (Weighted PROCOVA) that adjusts for both the mean and variance of the regression model using information obtained from the DTG. We prove that our method yields unbiased treatment effect estimators, and demonstrate via comprehensive simulation studies and case studies from Alzheimer's disease that it can reduce the variance of the treatment effect estimator, maintain the Type I error rate, and increase the power of the test for the treatment effect from 80% to 85%~90% when the variances from the DTG can explain 5%~10% of the variation in the RCT participants' outcomes.

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arXiv2023

A Bayesian Analysis of Two-Stage Randomized Experiments in the Presence of Interference, Treatment Nonadherence, and Missing Outcomes

Three critical issues for causal inference that often occur in modern, complicated experiments are interference, treatment nonadherence, and missing outcomes. A great deal of research efforts has been dedicated to developing causal inferential methodologies that address these issues separately. However, methodologies that can address these issues simultaneously are lacking. We propose a Bayesian causal inference methodology to address this gap. Our methodology extends existing causal frameworks and methods, specifically, two-staged randomized experiments and the principal stratification framework. In contrast to existing methods that invoke strong structural assumptions to identify principal causal effects, our Bayesian approach uses flexible distributional models that can accommodate the complexities of interference and missing outcomes, and that ensure that principal causal effects are weakly identifiable. We illustrate our methodology via simulation studies and a re-analysis of real-life data from an evaluation of India's National Health Insurance Program. Our methodology enables us to identify new active causal effects that were not identified in past analyses. Ultimately, our simulation studies and case study demonstrate how our methodology can yield more informative analyses in modern experiments with interference, treatment nonadherence, missing outcomes, and complicated outcome generation mechanisms.

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arXiv2022

Distributed Design for Causal Inferences on Big Observational Data

A fundamental issue in causal inference for Big Observational Data is confounding due to covariate imbalances between treatment groups. This can be addressed by designing the data prior to analysis. Existing design methods, developed for traditional observational studies with single designers, can yield unsatisfactory designs with suboptimum covariate balance for Big Observational Data due to their inability to accommodate the massive dimensionality, heterogeneity, and volume of the Big Data. We propose a new framework for the distributed design of Big Observational Data amongst collaborative designers. Our framework first assigns subsets of the high-dimensional and heterogeneous covariates to multiple designers. The designers then summarize their covariates into lower-dimensional quantities, share their summaries with the others, and design the study in parallel based on their assigned covariates and the summaries they receive. The final design is selected by comparing balance measures for all covariates across the candidates. We perform simulation studies and analyze datasets from the 2016 Atlantic Causal Inference Conference Data Challenge to demonstrate the flexibility and power of our framework for constructing designs with good covariate balance from Big Observational Data.

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arXiv2014

Inference for deformation and interference in 3D printing

Additive manufacturing, or 3D printing, is a promising manufacturing technique marred by product deformation due to material solidification in the printing process. Control of printed product deformation can be achieved by a compensation plan. However, little attention has been paid to interference in compensation, which is thought to result from the inevitable discretization of a compensation plan. We investigate interference with an experiment involving the application of discretized compensation plans to cylinders. Our treatment illustrates a principled framework for detecting and modeling interference, and ultimately provides a new step toward better understanding quality control for 3D printing.

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arXiv2014

Comments on the Neyman-Fisher Controversy and Its Consequences

The Neyman-Fisher controversy considered here originated with the 1935 presentation of Jerzy Neyman's Statistical Problems in Agricultural Experimentation to the Royal Statistical Society. Neyman asserted that the standard ANOVA F-test for randomized complete block designs is valid, whereas the analogous test for Latin squares is invalid in the sense of detecting differentiation among the treatments, when none existed on average, more often than desired (i.e., having a higher Type I error than advertised). However, Neyman's expressions for the expected mean residual sum of squares, for both designs, are generally incorrect. Furthermore, Neyman's belief that the Type I error (when testing the null hypothesis of zero average treatment effects) is higher than desired, whenever the expected mean treatment sum of squares is greater than the expected mean residual sum of squares, is generally incorrect. Simple examples show that, without further assumptions on the potential outcomes, one cannot determine the Type I error of the F-test from expected sums of squares. Ultimately, we believe that the Neyman-Fisher controversy had a deleterious impact on the development of statistics, with a major consequence being that potential outcomes were ignored in favor of linear models and classical statistical procedures that are imprecise without applied contexts.

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