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In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of…

The positivity assumption is central in the identification of a causal effect, and especially the stochastic variant is an issue many applied researchers face, yet is rarely discussed, especially in conjunction with continuous treatments or…

Applications · Statistics 2026-02-03 Katharina Ring , Michael Schomaker

An early phase clinical trial is the first step in evaluating the effects in humans of a potential new anti-disease agent or combination of agents. Usually called "phase I" or "phase I/II" trials, these experiments typically have the…

Methodology · Statistics 2010-12-01 Peter F. Thall

Most clinical prediction studies are developed from retrospective cohorts and reported as if all patient information were observed at once. In practice, clinicians face a more consequential question: \emph{when is there already enough…

Methodology · Statistics 2026-04-27 Hui-Mean Foo , Yuan-chin Ivan Chang

Randomized experiments often need to be stopped prematurely due to the treatment having an unintended harmful effect. Existing methods that determine when to stop an experiment early are typically applied to the data in aggregate and do not…

Methodology · Statistics 2023-10-31 Hammaad Adam , Fan Yin , Huibin , Hu , Neil Tenenholtz , Lorin Crawford , Lester Mackey , Allison Koenecke

A popular setting in medical statistics is a group sequential trial with independent and identically distributed normal outcomes, in which interim analyses of the sum of the outcomes are performed. Based on a prescribed stopping rule, one…

Statistics Theory · Mathematics 2018-04-03 Ben Berckmoes , Anna Ivanova , Geert Molenberghs

Clinical research should conform to high standards of ethical and scientific integrity, given that human lives are at stake. However, economic incentives can generate conflicts of interest for investigators, who may be inclined to withhold…

General Economics · Economics 2022-10-12 Jérôme Adda , Christian Decker , Marco Ottaviani

Clinical trials often allow patients in the control arm to switch to the treatment arm if their physical conditions are worse than certain tolerance levels. For instance, treatment switching arises in the Concorde clinical trial, which aims…

Applications · Statistics 2023-09-06 Alessandra Mattei , Peng Ding , Veronica Ballerini , Fabrizia Mealli

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

This paper extends my research applying statistical decision theory to treatment choice with sample data, using maximum regret to evaluate the performance of treatment rules. The specific new contribution is to study as-if optimization…

Econometrics · Economics 2021-10-05 Charles F. Manski

Pragmatic trials increasingly define outcomes using real-world data such as electronic health records, where assessments are collected during routine care rather than at fixed timepoints. Consequently, these uncontrolled assessments may be…

Estimating the long-term effects of treatments is of interest in many fields. A common challenge in estimating such treatment effects is that long-term outcomes are unobserved in the time frame needed to make policy decisions. One approach…

Methodology · Statistics 2024-08-23 Susan Athey , Raj Chetty , Guido Imbens , Hyunseung Kang

Typically, a randomized experiment is designed to test a hypothesis about the average treatment effect and sometimes hypotheses about treatment effect variation. The results of such a study may then be used to inform policy and practice for…

Methodology · Statistics 2026-05-01 Elizabeth Tipton , Michalis Mamakos

In a clinical trial with a survival outcome, an interim analysis is often performed to allow for early stopping for efficacy. If the interim analysis is early in the trial, one might conclude that a new treatment is more effective (compared…

Methodology · Statistics 2023-05-09 Marianne A Jonker , Steven Teerenstra

An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment…

The two-trials rule for drug approval requires "at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness". This is usually implemented by requiring two significant pivotal trials and is the…

Methodology · Statistics 2023-11-10 Leonhard Held

The first step towards investigating the effectiveness of a treatment via a randomized trial is to split the population into control and treatment groups then compare the average response of the treatment group receiving the treatment to…

Econometrics · Economics 2022-08-30 Hossein Babaei , Sina Alemohammad , Richard Baraniuk

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

A very classical problem in statistics is to test the stochastic superiority of one distribution to another. However, many existing approaches are developed for independent samples and, moreover, do not take censored data into account. We…

Methodology · Statistics 2023-06-19 Dennis Dobler , Kathrin Möllenhoff

The predictions from an accurate prognostic model can be of great interest to patients and clinicians. When predictions are reported to individuals, they may decide to take action to improve their health or they may simply be comforted by…

Quantitative Methods · Quantitative Biology 2019-09-10 Michael C Sachs , Arvid Sjölander , Erin E Gabriel