Toward a Semiparametric Efficiency Theory under Equality Constraints in Nested Markov Models

Probabilistic models of Directed Acyclic Graphs (DAGs) with latent variables impose equality constraints on the observed data distribution beyond ordinary conditional independencies. These so-called Verma constraints arise in nested Markov models associated with Acyclic Directed Mixed Graphs, the latent projection of latent-variable DAGs. While nested Markov models have been extensively studied from the perspectives of graphical representation and causal identification, their implications for semiparametric efficiency theory remain less understood. We develop results toward establishing a semiparametric framework for statistical models defined by Verma constraints. Our key observation is that nested Markov constraints admit weighted conditional-moment representations under post-fixing distributions induced by graphical fixing operations. We show that fixing induces weighted orthogonality relations in L2(P), thereby converting Verma constraints into explicit tangent-space restrictions. Building on this representation, we characterize the tangent-space orthocomplement for models defined by a single nested Markov constraint through residualized weighted moment functions. This geometric formulation yields Hilbert-space characterizations of semiparametric efficient influence functions and efficiency bounds via orthogonal projection and equivalent minimum-variance formulations. We further discuss extensions to models involving multiple nested Markov constraints, for which we characterize a subspace of the orthocomplement as sums of the corresponding weighted orthogonality relations, while leaving the complete tangent-space characterization open. More broadly, our results connect nested graphical structure with semiparametric Hilbert-space geometry and provide a foundation for a general efficiency theory for nested Markov models. We illustrate the framework through several latent-variable DAGs.

Longitudinal Adaptive Experimental Design for Learning Multiple Target Estimands with Semiparametric Efficient Inference

Adaptive designs are increasingly used in clinical trials and digital experiments to improve estimation efficiency by updating treatment randomization probabilities as data accumulate. While most existing work focuses on settings with a single-stage treatment, adaptive designs for longitudinal studies with multi-stage, time-varying treatments remain relatively underexplored. In this work, we develop a general semiparametric efficiency framework for designing longitudinal adaptive experiments to optimize the estimation efficiency of a broad class of target estimands of interest. An efficiency-oriented design criterion is proposed to accommodate both single-estimand targets and joint optimization across multiple estimands. We demonstrate that optimal randomization at earlier stages depends on later-stage allocations, yielding a backward-recursive strategy for deriving the oracle design, and propose a longitudinal adaptive design to sequentially learn and target the oracle design using accumulating data. We further develop an adaptive-design-likelihood-based longitudinal targeted maximum likelihood estimator (ADL-LTMLE) for asymptotically normal and semiparametric efficient estimation of statistical estimands from dependent data collected from adaptive experiments, without relying on parametric model assumptions. Applying the framework to time-to-treatment-initiation effects that compare initiating treatment at a given stage with delaying initiation until a subsequent stage, we show that designs optimized for a particular stage-specific effect can substantially compromise estimation efficiency for effects defined at other stages, highlighting the design trade-offs addressed by our framework. Simulation studies show the proposed design and estimation approaches achieve substantial variance reductions relative to non-adaptive designs, with performance close to that of the oracle design.

Augmented transfer regression learning for completely missing covariates

Large-scale population-level datasets, such as the UK Biobank and the All of Us Research Program, often lack covariates needed for a specific analysis, such as genetic or lifestyle measures, while related studies measure them. This creates a cross-population missing data problem in which covariates are completely unobserved in the target population, rather than partially missing within one dataset. We propose an augmented transfer regression learning method for this setting. The key identifying condition is a sub-population shift assumption: the joint distribution of the outcome and observed covariates may differ across source and target populations, but the conditional distribution of the missing covariates given observed variables is invariant. We combine importance-weighted estimating equations with imputation terms for first- and second-order moments of the missing covariates. The resulting estimator is doubly robust, remaining consistent if either the density ratio model or both imputation models are correctly specified. It is $n^{1/2}$-consistent and asymptotically normal, and attains the semiparametric efficiency bound when both nuisance models are correctly specified.