Iván Díaz

Richard Liu, Nicholas T. Williams, Kara E. Rudolph et al.

Causal mediation analyses investigate the mechanisms through which causes exert their effects, and are therefore central to scientific progress. The literature on the non-parametric definition and identification of mediational effects in rigourous causal models has grown significantly in recent years, and there has been important progress to address challenges in the interpretation and identification of such effects. Despite great progress in the causal inference front, statistical methodology for non-parametric estimation has lagged behind, with few or no methods available for tackling non-parametric estimation in the presence of multiple, continuous, or high-dimensional mediators. In this paper we show that the identification formulas for six popular non-parametric approaches to mediation analysis proposed in recent years can be recovered from just two statistical estimands. We leverage this finding to propose an all-purpose one-step estimation algorithm that can be coupled with machine learning in any mediation study that uses any of these six definitions of mediation. The estimators have desirable properties, such as $\sqrt{n}$-convergence and asymptotic normality. Estimating the first-order correction for the one-step estimator requires estimation of complex density ratios on the potentially high-dimensional mediators, a challenge that is solved using recent advancements in so-called Riesz learning. We illustrate the properties of our methods in a simulation study and illustrate its use on real data to estimate the extent to which pain management practices mediate the total effect of having a chronic pain disorder on opioid use disorder.

Jiacheng Ge, Iván Díaz

Conditional effects are commonly used measures for understanding how treatment effects vary across different groups, and are often used to target treatments/interventions to groups who benefit most. In this work we review existing methods and propose novel ones, focusing on the odds ratio (OR) and the risk ratio (RR). While estimation of the conditional average treatment effect (ATE) has been widely studied, estimators for the OR and RR lag behind, and cutting edge estimators such as those based on doubly robust transformations or orthogonal risk functions have not been generalized to these parameters. We propose such a generalization here, focusing on the DR-learner and the R-learner. We derive orthogonal risk functions for the OR and RR and show that the associated pseudo-outcomes satisfy second-order conditional-mean remainder properties analogous to the ATE case. We also evaluate estimators for the conditional ATE, OR, and RR in a comprehensive nonparametric Monte Carlo simulation study to compare them with common alternatives under hundreds of different data-generating distributions. Our numerical studies provide empirical guidance for choosing an estimator. For instance, they show that while parametric models are useful in very simple settings, the proposed nonparametric estimators significantly reduce bias and mean squared error in the more complex settings expected in the real world. We illustrate the methods in the analysis of physical activity and sleep trouble in U.S. adults using data from the National Health and Nutrition Examination Survey (NHANES). The results demonstrate that our estimators uncover substantial treatment effect heterogeneity that is obscured by traditional regression approaches and lead to improved treatment decision rules, highlighting the importance of data-adaptive methods for advancing precision health research.

Sajjad Ahmed, Alexander Kropotov, Roberto Ignacio Genovese et al.

The Barcelona Zetascale Lab (BZL) project aims to strengthening Europe's capacity in the design and manufacture of RISC-V based high-performance computing chips. In this context, we present a holistic pre-silicon verification and validation (V&V) methodology targeting highly robust RISC-V chip designs. This paper provides an overview of BZL's V&V approach, which integrates three complementary platforms: (1) a UVM-based verification environment to thoroughly validate RTL functionality; (2) an FPGA-based validation platform that enables system-level pre-silicon hardware-software RTL validation; and (3) a CI/CD flow that continuously automates build, deployment, and tests across these domains. By embedding these platforms into an industrial-grade V&V loop and exploiting large-scale CPU and FPGA hardware infrastructures, the BZL project enables continuous evolution of reliable hardware development and software integration. We believe that the BZL's V&V flow represents a robust and scalable foundation for ensuring the pre-silicon functional correctness and system level validation of RISC-V chip designs, and can serve as a key enabler for strategic initiatives in Europe, such as EPI and DARE, and beyond.

Iván Díaz

The consistency of doubly robust estimators relies on consistent estimation of at least one of two nuisance regression parameters. In moderate to large dimensions, the use of flexible data-adaptive regression estimators may aid in achieving this consistency. However, $n^{1/2}$-consistency of doubly robust estimators is not guaranteed if one of the nuisance estimators is inconsistent. In this paper we present a doubly robust estimator for survival analysis with the novel property that it converges to a Gaussian variable at $n^{1/2}$-rate for a large class of data-adaptive estimators of the nuisance parameters, under the only assumption that at least one of them is consistently estimated at a $n^{1/4}$-rate. This result is achieved through adaptation of recent ideas in semiparametric inference, which amount to: (i) Gaussianizing (i.e., making asymptotically linear) a drift term that arises in the asymptotic analysis of the doubly robust estimator, and (ii) using cross-fitting to avoid entropy conditions on the nuisance estimators. We present the formula of the asymptotic variance of the estimator, which allows computation of doubly robust confidence intervals and p-values. We illustrate the finite-sample properties of the estimator in simulation studies, and demonstrate its use in a phase III clinical trial for estimating the effect of a novel therapy for the treatment of HER2 positive breast cancer.