Searcharxiv⌕ Search
Home/Archive/arXiv

arXiv · 2511.09353

Designing Efficient Hybrid and Single-Arm Trials: External Control Borrowing and Sample Size Calculation

Yujing Gao·Xiang Zhang·Shu Yang
View original source ↗Read source document ↗Export metadata ↓

Abstract

External controls (ECs) from historical trials or real-world data have gained increasing attention as a way to augment hybrid and single-arm trials, especially when balanced randomization is infeasible. While most existing work has focused on post-trial inference using ECs, their role in prospective trial design remains less explored. We address this gap by focusing on the sample size determination and power analysis for an experimental design problem that encompasses standard randomized controlled trials (RCTs), hybrid trials, and single-arm trials. Building on estimators derived from the efficient influence function, we develop hybrid and single-arm design strategies that leverage comparable EC data to reduce the required sample size of the current study. We derive asymptotic variance expressions for these estimators in terms of interpretable, population-level quantities and introduce a pre-experimental variance estimation procedure to guide sample size calculation, ensuring prespecified type I error and power for the relevant hypothesis test. Simulation studies demonstrate that the proposed hybrid and single-arm designs maintain valid type I error and achieve target power across diverse scenarios while requiring substantially fewer subjects in the current study than RCT designs. A real data application further illustrates the practical utility and advantages of the proposed hybrid and single-arm designs.

Explore related subjects

stat.MEstat.AP

Keep this discovery

BibTeXRIS

Yujing Gao, Xiang Zhang, Shu Yang. 2025-11-12. Designing Efficient Hybrid and Single-Arm Trials: External Control Borrowing and Sample Size Calculation. https://arxiv.org/abs/2511.09353

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Surprise Reduction and Nullification in Bayesian and Inverse Bayesian Inference under Ambiguous Prediction-Error Attribution

In non-stationary environments, prediction errors may signal environmental change or transient outliers, and adaptive systems must track such changes without overreacting to outliers. We distinguish surprise reduction, which updates beliefs to fit observations, from surprise nullification, which weakens constraints imposed by the predictive structure, and formalize both within Bayesian and inverse Bayesian (BIB) inference. Belief and likelihood updates are derived from variational objectives sharing a nullification strength, determined endogenously by minimizing surprise under the candidate post-update predictive distribution. In the Gaussian case, nullification expands belief and likelihood variances by a common factor relative to standard Bayesian updating, leaving the ratio unchanged. BIB thus defers attribution of the prediction error, committing to neither latent-state change nor observation-process uncertainty. The nullification strength is carried over as a candidate and is maintained or released according to the predictive surprise of the next observation. In a mean estimation task with outliers and changepoints, no scanned parameter setting of a Sage-Husa-type adaptive Kalman filter, fixed-strength BIB variant, or belief-forgetting-only variant outperforms BIB in both changepoint tracking and post-outlier stability. An oracle-informed reduced Bayesian model tracks changepoints better but is less stable after outliers. Although BIB maintains no explicit hypotheses about changepoints or outliers, it generates event-dependent dynamics. The learning rate increases after changepoints, whereas after outliers, nullification is released, and this increase is suppressed. Deferring attribution and letting subsequent observations differentiate the responses may constitute a principle of adaptive inference in non-stationary environments.

stat.ME↗
arXiv2026

Generalized Ridge Refitting for the Lasso and Prediction Improvement Bounds

We study a class of Lasso based estimators obtained by applying a quadratic correction on the Lasso equicorrelation set. The penalty matrix determines both the magnitude and geometry of the correction and contains, among other cases, the isotropic Lasso--Ridge correction, least squares refitting, Gram proportional interpolation between the Lasso and least squares, and coordinate specific penalties. We first derive a closed form representation and isolate the positive gain component of the resulting prediction improvement. We then control the remaining stochastic linear term in expectation by localizing the random signed equicorrelation model around a deterministic reference support. This yields a finite sample expectation bound that explicitly accounts for the randomness induced by Lasso model selection. The resulting decomposition provides a unified framework for understanding when Lasso based quadratic corrections can improve prediction.

stat.ME↗
arXiv2026

Discretization in covariate-adaptive randomization: gains and losses

Covariate-adaptive randomization(CAR) is widely implemented in clinical trials to balance prognostic covariates across treatment arms. Continuous covariates are often discretized into strata in practice, yet their consequences are not clearly understood. This paper provides a comprehensive study of the impact of discretization on both the CAR design process and the inferential results thereafter. We establish the asymptotic properties of both imbalance measures and treatment effect estimators under discretized and non-discretized settings. Practical recommendations are given on when and how discretization should be employed. We show that discretization in design is generally recommended, as it enhances robustness against model misspecification. However, if the true model is known, the most efficient strategy is to balance covariates according to that model in the design. The theoretical results are corroborated by extensive simulation studies and an empirical application to a diabetes trial dataset. Together, the results clarify the gains and losses of discretization in CAR and pave the way for learning impact of discretization to other designs and beyond.

stat.ME↗