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Pilot feasibility studies play a pivotal role in the development of clinical trials for rare diseases, where small populations and slow recruitment often threaten trial viability. While such studies are commonly used to assess operational…

Applications · Statistics 2025-07-15 Lara Maleyeff , Valérie Leclair , Shirin Golchi , Marie Hudson

External pilot trials of complex interventions are used to help determine if and how a confirmatory trial should be undertaken, providing estimates of parameters such as recruitment, retention and adherence rates. The decision to progress…

Randomized trials are widely considered as the gold standard for evaluating the effects of decision policies. Trial data is, however, drawn from a population which may differ from the intended target population and this raises a problem of…

Methodology · Statistics 2024-10-30 Sofia Ek , Dave Zachariah

In situations where it is difficult to enroll patients in randomized controlled trials, external data can improve efficiency and feasibility. In such cases, adaptive trial designs could be used to decrease enrollment in the control arm of…

Methodology · Statistics 2020-10-02 Brian D. Segal , W. Katherine Tan

Generalizability and transportability methods have been proposed to address the external validity bias of randomized clinical trials that results from differences in the distribution of treatment effect modifiers between trial and target…

Practical employment of Bayesian trial designs is still rare. Even if accepted in principle, the regulators have commonly required that such designs be calibrated according to an upper bound for the frequentist type I error rate. This…

Methodology · Statistics 2026-03-25 Elja Arjas , Dario Gasbarra

Augmenting the control arm in clinical trials with external data can improve statistical power for demonstrating treatment effects. In many time-to-event outcome trials, participants are subject to truncation by death. Direct application of…

Methodology · Statistics 2025-06-24 Zehao Su , Helene C. W. Rytgaard , Henrik Ravn , Frank Eriksson

Leveraging external controls -- relevant individual patient data under control from external trials or real-world data -- has the potential to reduce the cost of randomized controlled trials (RCTs) while increasing the proportion of trial…

Methodology · Statistics 2022-07-13 Yanyao Yi , Ying Zhang , Yu Du , Ting Ye

A new approach to adaptive design of clinical trials is proposed in a general multiparameter exponential family setting, based on generalized likelihood ratio statistics and optimal sequential testing theory. These designs are easy to…

Statistics Theory · Mathematics 2011-05-25 Jay Bartroff , Tze Leung Lai

Determination of posterior probability for go-no-go decision and predictive power are becoming increasingly common for resource optimization in clinical investigation. There are vast published literature on these topics; however, the…

Methodology · Statistics 2023-02-09 Madan G. Kundu , Sandipan Samanta , Shoubhik Mondal

Randomized clinical trials are considered the gold standard for informing treatment guidelines, but results may not generalize to real-world populations. Generalizability is hindered by distributional differences in baseline covariates and…

Methodology · Statistics 2025-06-03 Rachael K. Ross , Ivan Diaz , Amy J. Pitts , Elizabeth A. Stuart , Kara E. Rudolph

In this paper, we propose a general method for testing composite hypotheses. Our idea is to use confidence limits to define stopping and decision rules. The requirements of operating characteristic function can be satisfied by adjusting the…

Statistics Theory · Mathematics 2012-02-10 Xinjia Chen

When assessing causal effects, determining the target population to which the results are intended to generalize is a critical decision. Randomized and observational studies each have strengths and limitations for estimating causal effects…

Methodology · Statistics 2022-10-21 Irina Degtiar , Sherri Rose

In recent years, real-world external controls have grown in popularity as a tool to empower randomized placebo-controlled trials, particularly in rare diseases or cases where balanced randomization is unethical or impractical. However, as…

Methodology · Statistics 2024-11-14 Chenyin Gao , Shu Yang , Mingyang Shan , Wenyu Ye , Ilya Lipkovich , Douglas Faries

Pilot studies are highly recommended in experiments with animals when little is known about the anticipated values of the mean of the variable under study, its variance or the probability of response. They are also recommended to test the…

Applications · Statistics 2018-03-20 C. O. S. Sorzano , D. Tabas-Madrid , F. Núñez , C. Fernández-Criado , A. Naranjo

Physical experiments in the national security domain are often expensive and time-consuming. Test engineers must certify the compatibility of aircraft and their weapon systems before they can be deployed in the field, but the testing…

Methodology · Statistics 2023-10-02 Daniel Ries , Victoria R. C. Sieck , Philip Jones , Julie Shaffer

The front-door criterion can be used to identify and compute causal effects despite the existence of unmeasured confounders between a treatment and outcome. However, the key assumptions -- (i) the existence of a variable (or set of…

Methodology · Statistics 2022-06-20 Rohit Bhattacharya , Razieh Nabi

We consider the problem of estimating personalized treatment policies that are "externally valid" or "generalizable": they perform well in target populations that differ from the experimental (or training) population from which the data are…

Econometrics · Economics 2025-11-10 Christopher Adjaho , Timothy Christensen

Suppose we are interested in the effect of a treatment in a clinical trial. The efficiency of inference may be limited due to small sample size. However, external control data are often available from historical studies. Motivated by an…

Methodology · Statistics 2021-12-10 Xinyu Li , Wang Miao , Fang Lu , Xiao-Hua Zhou

The use of patient-level information from previous studies, registries, and other external datasets can support the analysis of single-arm and randomized controlled trials to evaluate and test experimental treatments. However, the…

Methodology · Statistics 2025-10-23 Gopal Kotecha , Daniel E. Schwartz , Steffen Ventz , Lorenzo Trippa
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