arXiv subjects

Demissie Alemayehu

Publications and source records attributed to Demissie Alemayehu.

7 recordsLinked to original sources

arXiv2026

Sharp Decoupling Inequalities for the Variances and Second Moments of Sums of Dependent Random Variables

Both complete decoupling and tangent decoupling are classical tools aiming to compare two random processes where one has a weaker dependence structure. We give a new proof for the complete decoupling inequality, which provides a lower bound for the sum of dependent square-integrable nonnegative random variables $\sum\limits^n_{i=1} d_i$ \[ \frac{1}{2} \mathbb E \left( \sum\limits^n_{i=1} z_i \right)^2 \leq \mathbb E \left( \sum\limits^n_{i=1} d_i \right)^2, \] where $z_i \stackrel{\mathcal{L}}{=} d_i$ for all $i\leq n$ and $z_i$'s are mutually independent. We will then provide the following sharp tangent decoupling inequalities \[\mathbb Var \left( \sum\limits^n_{i=1} d_i\right) \leq 2 \mathbb Var \left( \sum\limits^n_{i=1} e_i\right),\] and \[\mathbb E \left( \sum\limits^n_{i=1} d_i\right)^2 \leq 2 \mathbb E \left( \sum\limits^n_{i=1} e_i\right)^2 - \left[ \mathbb E \left( \sum\limits^n_{i=1} e_i\right) \right]^2,\] where $\{e_i\}$ is the decoupled sequences of $\{d_i\}$ and $d_i$'s are not forced to be nonnegative. Applications to construct Chebyshev-type inequality and Paley-Zygmund-type inequality, and to bound the second moments of randomly stopped sums will be provided.

math.PR↗

arXiv2026

From Cumulative Weights to Marginal Density Ratios: Per-Protocol Estimation in Sequential Target Trial Emulation

Sequential target trial emulation evaluates eligibility at multiple baseline times to emulate a sequence of randomized trials using observational data. Estimating per-protocol effects in this setting is challenging because treatment deviations and loss to follow-up induce selection among individuals who remain observed and adherent over time. Conventional inverse-probability methods address this selection using cumulative weights constructed from estimated adherence and censoring probabilities, but these weights can be highly variable, leading to unstable and imprecise effect estimates. We propose a different approach based on marginal density ratios (MDRs). The MDR directly compares the state distribution among individuals who would remain event-free under a target treatment strategy with the corresponding distribution among observed-adherent individuals. We use longitudinal g-computation to generate the target risk sets and a probabilistic classifier to estimate density ratios for reweighting the observed outcomes. Building on this approach, we also develop a doubly robust extension. Favorable performance across the simulation study suggests that MDR weighting is a promising alternative to cumulative longitudinal weights when its identification assumptions are plausible.

stat.ME↗

arXiv2026

Towards Best Practices for Covariate Adjustment in Regulatory Trials: From Fixed to Data-Adaptive Approaches

While randomization justifies the use of unadjusted effect estimators in randomized trials, there is growing interest in covariate adjustment to improve precision. Adjusting for baseline variables that are prognostic of the outcome can reduce estimator variance, resulting in narrower confidence intervals and increased statistical power. Recent guidance by the U.S. Food and Drug Administration supports fixed adjustment for prognostic covariates using parametric regression models. However, this guidance does not address more flexible approaches using data-adaptive or machine learning methods. We offer our perspectives on covariate adjustment to improve analytic precision. We focus on estimating the average effect for the target population in trials with minimal outcome missingness. We provide a non-technical overview of effect estimators that are unadjusted and effect estimators using fixed versus data-adaptive adjustment. We offer practical suggestions for conducting adjusted analyses that are data-adaptive, fully pre-specified, transparently and reproducibly implemented, robust to model misspecification, and guaranteed to improve precision relative to unadjusted analyses --- all while preserving statistical validity and the causal effect of interest. We hope that sharing our perspectives will foster broader discussion and eventual acceptance of principled, pre-specified, data-adaptive covariate adjustment in randomized trials.

stat.ME↗

arXiv2026

Mitigating the Winner's Curse While Controlling Multiplicity: e-Process Methods for Anytime-Valid Inference in Dose-Ranging Trials

Phase II dose-ranging trials often report the largest observed dose-control effect while inspecting accumulating data repeatedly. This creates two coupled distortions: selection optimism from choosing the empirical winner, known as the winner's curse, and Type I error inflation from multiplicity across doses and interim looks. We develop an anytime-valid procedure for testing whether the best true dose effect exceeds a clinically meaningful margin. The mathematical starting point is a recent selection-premium identity for the running maximum: for dose-control scores, the expected gain from re-selecting the current leader becomes a predictable selection charge. Subtracting this charge gives a residual with nonpositive drift under the composite null; applying a one-sided mixture-exponential construction then yields an e-process and hence an anytime-valid global test. The resulting rule has a transparent ledger form: raw best effect minus selection charge minus monitoring margin, and a ``GO'' decision is made only when the remaining evidence still exceeds the clinical margin. We give plug-in implementations for Gaussian and binary outcomes, prove finite-sample Type I control and anytime lower confidence bounds for the best dose effect, and illustrate the method through a worked example and simulations.

stat.ME↗

arXiv2026

Advancing Evidence Generation in Biomedical Research Using Natural Hermite and Propensity Score Indices: Applications to External Control Arms

When it is not feasible to conduct randomized controlled trials (RCTs), the use of external control arms based on real-world data (RWD) may be a viable option. However, challenges arising from data heterogeneity must be addressed to ensure the reliability of trial results. We consider the use of Natural Hermite and propensity score indices to facilitate robust comparisons between RCTs and RWD studies. Illustrations are provided on the implementation and performance of the underlying algorithms using simulated data, as well as synthetic data from a clinical trial and RWD.

stat.AP↗

arXiv2023

A Causal Roadmap for Generating High-Quality Real-World Evidence

Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies, and industry. A broad spectrum of studies use real-world data (RWD) to produce RWE, ranging from randomized controlled trials with outcomes assessed using RWD to fully observational studies. Yet many RWE study proposals lack sufficient detail to evaluate adequacy, and many analyses of RWD suffer from implausible assumptions, other methodological flaws, or inappropriate interpretations. The Causal Roadmap is an explicit, itemized, iterative process that guides investigators to pre-specify analytic study designs; it addresses a wide range of guidance within a single framework. By requiring transparent evaluation of causal assumptions and facilitating objective comparisons of design and analysis choices based on pre-specified criteria, the Roadmap can help investigators to evaluate the quality of evidence that a given study is likely to produce, specify a study to generate high-quality RWE, and communicate effectively with regulatory agencies and other stakeholders. This paper aims to disseminate and extend the Causal Roadmap framework for use by clinical and translational researchers, with companion papers demonstrating application of the Causal Roadmap for specific use cases.

stat.ME↗

arXiv2023

Prediction and estimation of random variables with infinite mean or variance

In this paper we propose an optimal predictor of a random variable that has either an infinite mean or an infinite variance. The method consists of transforming the random variable such that the transformed variable has a finite mean and finite variance. The proposed predictor is a generalized arithmetic mean which is similar to the notion of certainty price in utility theory. Typically, the transformation consists of a parametric family of bijections, in which case the parameter might be chosen to minimize the prediction error in the transformed coordinates. The statistical properties of the estimator of the proposed predictor are studied, and confidence intervals are provided. The performance of the procedure is illustrated using simulated and real data.

math.ST↗