arXiv subjects

Jens Magelund Tarp

Publications and source records attributed to Jens Magelund Tarp.

9 recordsLinked to original sources

arXiv2026

Frugal, Flexible, Faithful: Causal Data Simulation via Frengression

Machine learning has revitalized causal inference by combining flexible models and principled estimators, yet robust benchmarking and evaluation remain challenging with real-world data. In this work, we introduce frengression, a deep generative realization of the frugal parameterization that models the joint distribution of covariates, treatments and outcomes around the causal margin of interest. Frengression provides accurate estimation and flexible, faithful simulation of multivariate, time-varying data; it also enables direct sampling from user-specified interventional distributions. Model consistency and extrapolation guarantees are established, with validation on real-world clinical trial data demonstrating frengression's practical utility. We envision this framework sparking new research into generative approaches for causal margin modelling.

stat.ME↗

arXiv2026

Causal-ICM: A Data Fusion Framework For Heterogeneous Treatment Effect Estimation With Multi-Task Gaussian Processes

Bridging the gap between internal and external validity is crucial for heterogeneous treatment effect estimation. Randomised controlled trials (RCTs), favoured for their internal validity due to randomisation, often encounter challenges in generalising findings due to strict eligibility criteria. Observational studies, on the other hand, may provide stronger external validity through larger and more representative samples but can suffer from compromised internal validity due to unmeasured confounding. Motivated by these complementary characteristics, we propose a novel Bayesian nonparametric approach, Causal-ICM, leveraging multi-task Gaussian processes to integrate data from both RCTs and observational studies. In particular, we introduce a parameter that controls the degree of borrowing between the datasets and prevents the observational dataset from dominating the estimation. We propose a data-adaptive procedure for choosing the optimal value of the parameter. Causal-ICM outperforms other data fusion methods in point estimation across the covariate support of the observational study and provides principled uncertainty quantification for the estimated treatment effects. We demonstrate the robust performance of Causal-ICM in diverse scenarios through multiple simulation studies and a real-world study.

stat.ME↗

arXiv2026

Experiment-selector cross-validated targeted maximum likelihood estimator for hybrid RCT-external data studies

Augmenting a randomized controlled trial (RCT) with external data may increase power at the risk of introducing bias. To select and analyze the experiment (RCT alone or combined with external data) with the optimal bias-variance tradeoff, we develop a novel experiment-selector cross-validated targeted maximum likelihood estimator for randomized-external data studies (ES-CVTMLE). This estimator utilizes two estimates of bias to determine whether to integrate external data based on 1) a function of the difference in conditional mean outcome under control between the RCT and combined experiments and 2) an estimate of the average treatment effect on a negative control outcome (NCO). We define the asymptotic distribution of the ES-CVTMLE under varying magnitudes of bias and construct confidence intervals by Monte Carlo simulation. We evaluate ES-CVTMLE compared to three other data fusion estimators in simulations and demonstrate the ability of ES-CVTMLE to distinguish biased from unbiased external controls in a real data analysis of the effect of liraglutide on glycemic control from the LEADER trial. The ES-CVTMLE has the potential to improve power while providing relatively robust inference for future hybrid RCT-external data studies.

stat.ME↗

arXiv2025

Exact Simulation of Longitudinal Data from Marginal Structural Models

Simulating longitudinal data from specified marginal structural models is a crucial but challenging task for evaluating causal inference methods and informing study design. While data generation typically proceeds in a fully conditional manner using structural equations according to a temporal ordering, it is difficult to ensure alignment between conditional distributions and the target marginal causal effects, which presents a fundamental challenge. To address this, we propose a flexible and efficient algorithm for simulating longitudinal data that adheres exactly to a specified marginal structural model. Our approach accommodates time-to-event outcomes and extends naturally to survival settings, which are prevalent in applied research. Compared to existing approaches, it offers several advantages: it enables exact simulation from a known causal model rather than relying on approximations; avoids restrictive assumptions about the data-generating process; and remains computationally efficient by requiring only the evaluation of analytical expressions, rather than Monte Carlo methods or numerical integration. Through simulation studies replicating realistic scenarios, we validate the method's accuracy and utility. Our method will facilitate researchers in effectively simulating data with target causal structures for their specific scenarios.

stat.ME↗

arXiv2025

Adaptive-TMLE for the Average Treatment Effect based on Randomized Controlled Trial Augmented with Real-World Data

We consider the problem of estimating the average treatment effect (ATE) when both randomized control trial (RCT) data and external real-world data (RWD) are available. We decompose the ATE estimand as the difference between a pooled-ATE estimand that integrates RCT and RWD and a bias estimand that captures the conditional effect of RCT enrollment on the outcome. We introduce an adaptive targeted maximum likelihood estimation (A-TMLE) framework to estimate them. We prove that the A-TMLE estimator is root-n-consistent and asymptotically normal. Moreover, in finite sample, it achieves the super-efficiency one would obtain had one known the oracle model for the conditional effect of the RCT enrollment on the outcome. Consequently, the smaller and more parsimonious the working model of the bias induced by the RWD is, the greater our estimator's efficiency, while our estimator will always be at least as efficient as an efficient estimator that uses the RCT data only. A-TMLE outperforms existing methods in simulations by having smaller mean-squared-error and 95% confidence intervals. We apply A-TMLE to augment the DEVOTE trial with external data from the Optum Clinformatics Data Mart, demonstrating its potential to establish treatment superiority in noninferiority trials. A-TMLE could utilize external RWD to help improve the power of randomized trials without biasing the estimates of intervention effects. This approach could allow for smaller, faster trials, decreasing the time until patients can receive effective treatments.

stat.ME↗

arXiv2024

Data fusion for efficiency gain in ATE estimation: A practical review with simulations

The integration of real-world data (RWD) and randomized controlled trials (RCT) is increasingly important for advancing causal inference in scientific research. This combination holds great promise for enhancing the efficiency of causal effect estimation, offering benefits such as reduced trial participant numbers and expedited drug access for patients. Despite the availability of numerous data fusion methods, selecting the most appropriate one for a specific research question remains challenging. This paper systematically reviews and compares these methods regarding their assumptions, limitations, and implementation complexities. Through simulations reflecting real-world scenarios, we identify a prevalent risk-reward trade-off across different methods. We investigate and interpret this trade-off, providing key insights into the strengths and weaknesses of various methods; thereby helping researchers navigate through the application of data fusion for improved causal inference.

stat.ME↗

arXiv2024

Combining experimental and observational data through a power likelihood

Randomized controlled trials are the gold standard for causal inference and play a pivotal role in modern evidence-based medicine. However, the sample sizes they use are often too limited to draw significant causal conclusions for subgroups that are less prevalent in the population. In contrast, observational data are becoming increasingly accessible in large volumes but can be subject to bias as a result of hidden confounding. Given these complementary features, we propose a power likelihood approach to augmenting RCTs with observational data to improve the efficiency of treatment effect estimation. We provide a data-adaptive procedure for maximizing the expected log predictive density (ELPD) to select the learning rate that best regulates the information from the observational data. We validate our method through a simulation study that shows increased power while maintaining an approximate nominal coverage rate. Finally, we apply our method in a real-world data fusion study augmenting the PIONEER 6 clinical trial with a US health claims dataset, demonstrating the effectiveness of our method and providing detailed guidance on how to address practical considerations in its application.

stat.ME↗

arXiv2023

A Causal Roadmap for Hybrid Randomized and Real-World Data Designs: Case Study of Semaglutide and Cardiovascular Outcomes

Introduction: Increasing interest in real-world evidence has fueled the development of study designs incorporating real-world data (RWD). Using the Causal Roadmap, we specify three designs to evaluate the difference in risk of major adverse cardiovascular events (MACE) with oral semaglutide versus standard-of-care: 1) the actual sequence of non-inferiority and superiority randomized controlled trials (RCTs), 2) a single RCT, and 3) a hybrid randomized-external data study. Methods: The hybrid design considers integration of the PIONEER 6 RCT with RWD controls using the experiment-selector cross-validated targeted maximum likelihood estimator. We evaluate 95% confidence interval coverage, power, and average patient-time during which participants would be precluded from receiving a glucagon-like peptide-1 receptor agonist (GLP1-RA) for each design using simulations. Finally, we estimate the effect of oral semaglutide on MACE for the hybrid PIONEER 6-RWD analysis. Results: In simulations, Designs 1 and 2 performed similarly. The tradeoff between decreased coverage and patient-time without the possibility of a GLP1-RA for Designs 1 and 3 depended on the simulated bias. In real data analysis using Design 3, external controls were integrated in 84% of cross-validation folds, resulting in an estimated risk difference of -1.53%-points (95% CI -2.75%-points to -0.30%-points). Conclusions: The Causal Roadmap helps investigators to minimize potential bias in studies using RWD and to quantify tradeoffs between study designs. The simulation results help to interpret the level of evidence provided by the real data analysis in support of the superiority of oral semaglutide versus standard-of-care for cardiovascular risk reduction.

stat.AP↗

arXiv2013

Rotation induced grain growth and stagnation in phase field crystal models

We consider the grain growth and stagnation in polycrystalline microstructures. From the phase field crystal modelling of the coarsening dynamics, we identify a transition from a grain-growth stagnation upon deep quenching below the melting temperature $T_m$ to a continuous coarsening at shallower quenching near $T_m$. The grain evolution is mediated by local grain rotations. In the deep quenching regime, the grain assembly typically reaches a metastable state where the kinetic barrier for recrystallization across boundaries is too large and grain rotation with subsequent coalescence is infeasible. For quenching near $T_m$, we find that the grain growth depends on the average rate of grain rotation, and follows a power law behavior with time with a scaling exponent that depends on the quenching depth.

cond-mat.mtrl-sci↗