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In single-arm phase II oncology trials, the most popular choice of design is Simon's two-stage design, which allows early stopping at one interim analysis. However, the expected trial sample size can be reduced further by allowing…

Methodology · Statistics 2019-09-09 Martin Law , Michael J. Grayling , Adrian P. Mander

In small sample studies with binary outcome data, use of a normal approximation for hypothesis testing can lead to substantial inflation of the type-I error-rate. Consequently, exact statistical methods are necessitated, and accordingly,…

Methodology · Statistics 2017-11-29 Michael Grayling , Adrian Mander , James Wason

When a novel treatment has successfully passed phase I, different options to design subsequent phase II trials are available. One approach is a single-arm trial, comparing the response rate in the intervention group against a fixed…

Methodology · Statistics 2020-08-03 Johannes Krisam , Dorothea Weber , Richard F. Schlenk , Meinhard Kieser

Purpose: Two-stage single-arm trial designs are commonly used in phase II oncology to infer treatment effects for a binary primary outcome (e.g., tumour response). It is imperative that such studies be designed, analysed, and reported…

Applications · Statistics 2020-07-09 Michael J. Grayling , Adrian P. Mander

In this paper, we consider an experimental setting where units enter the experiment sequentially. Our goal is to form stopping rules which lead to estimators of treatment effects with a given precision. We propose a fixed-width confidence…

Statistics Theory · Mathematics 2024-05-07 Mattias Nordin , Mårten Schultzberg

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

Minimizing the number of patients exposed to potentially harmful drugs in early onco logical trials is a major concern during planning. Adaptive designs account for the inherent uncertainty about the true effect size by determining the…

Applications · Statistics 2016-05-03 Kevin Kunzmann , Meinhard Kieser

In this paper we apply a two-stage sequential design to item calibration problems under a three-parameter logistic model assumption. The measurement errors of the estimates of the latent trait levels of examinees are considered in our…

Applications · Statistics 2013-05-23 Yuan-chin Ivan Chang

Group sequential designs drive innovation in clinical, industrial, and corporate settings. Early stopping for failure in sequential designs conserves experimental resources, whereas early stopping for success accelerates access to improved…

Methodology · Statistics 2025-11-27 Luke Hagar , Shirin Golchi , Marina B. Klein

We propose a two-stage design for a clinical trial with an early stopping rule for safety. We use different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly…

Methodology · Statistics 2013-07-25 Daniel Zelterman

Sequential Bayesian experimental design typically assumes that the number of experiments is fixed before data collection begins. In practical campaigns, however, experimentation may need to terminate early because additional measurements…

Methodology · Statistics 2026-05-29 Chen Cheng , Xun Huan

The primary analysis in two-arm clinical trials usually involves inference on a scalar treatment effect parameter; e.g., depending on the outcome, the difference of treatment-specific means, risk difference, risk ratio, or odds ratio. Most…

Methodology · Statistics 2022-04-25 Anastasios A. Tsiatis , Marie Davidian

The win ratio is increasingly used in randomized trials due to its intuitive clinical interpretation, ability to incorporate the relative importance of composite endpoints, and its capacity for combining different types of outcomes (e.g.…

Methodology · Statistics 2026-02-02 Tracy Bergemann , Tim Hanson

Group sequential designs in clinical trials allow for interim efficacy and futility monitoring. Adjustment for baseline covariates can increase power and precision of estimated effects. However, inconsistently applying covariate adjustment…

Methodology · Statistics 2023-08-11 Marlena S. Bannick , Sonya L. Heltshe , Noah Simon

Background: trials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, TB and Hepatitis--C. However, standard non-inferiority designs have several limitations,…

Clinical trials are an instrument for making informed decisions based on evidence from well-designed experiments. Here we consider adaptive designs mainly from the perspective of multi-arm Phase II clinical trials, in which one or more…

Methodology · Statistics 2021-08-31 Elja Arjas , Dario Gasbarra

We consider the sequential experimental design problem in the predict-then-optimize paradigm. In this paradigm, the outputs of the prediction model are used as coefficient vectors in a downstream linear optimization problem. Traditional…

Machine Learning · Statistics 2026-02-06 Beichen Wan , Mo Liu , Paul Grigas , Zuo-Jun Max Shen

Sequential trial design is an important statistical approach to increase the efficiency of clinical trials. Bayesian sequential trial design relies primarily on conducting a Monte Carlo simulation under the hypotheses of interest and…

Methodology · Statistics 2025-12-01 Riko Kelter , Samuel Pawel

Due to the high cost and high failure rate of Phase III trials, seamless Phase II/III designs are more and more popular to trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior…

Applications · Statistics 2022-06-28 Guanhong Miao , Jason J. Z. Liao , Jing Yang , Keaven Anderson

2-in-1 design (Chen et al. 2018) is becoming popular in oncology drug development, with the flexibility of using different endpoints at different decision time. Based on the observed interim data, sponsors choose either to seamlessly…

Methodology · Statistics 2024-04-15 Runjia Li , Liwen Wu , Rachael Liu , Jianchang Lin
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