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The proximal causal inference framework enables the identification and estimation of causal effects in the presence of unmeasured confounding by leveraging two disjoint sets of observed strong proxies: negative control treatments and…

Methodology · Statistics 2025-12-16 Antonio Olivas-Martinez , Peter B. Gilbert , Andrea Rotnitzky

Estimating causal effects in a target population with unmeasured confounders is challenging, especially when instrumental variables (IVs) are unavailable. However, IVs from auxiliary populations with similar problems can help infer causal…

Methodology · Statistics 2025-08-06 Wei Li , Jiapeng Liu , Peng Ding , Zhi Geng

Nonlinear longitudinal proportional effect models have been proposed to improve power and provide direct estimates of the proportional treatment effect in randomized clinical trials. These models assume a fixed proportional treatment effect…

Methodology · Statistics 2026-01-23 Michael C. Donohue , Philip S. Insel , Oliver Langford

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

We conducted a systematic comparison of statistical methods used for the analysis of time-to-event outcomes under various proportional and nonproportional hazard (NPH) scenarios. Our study used data from recently published oncology trials…

Applications · Statistics 2025-02-12 Xinyu Zhang , Erich J. Greene , Ondrej Blaha , Wei Wei

Background: The Cox model and its extensions assuming proportional hazards is widely used to estimate vaccine efficacy (VE). In the typical situation that VE wanes over time, the VE estimates are not only sensitive to study duration and…

Applications · Statistics 2025-09-10 Ziwei Zhao , Xiangmei Ma , Paul Milligan , Yin Bun Cheung

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

Human understanding of randomness and variation is shaped by a number of cognitive biases. Here we relate a lesser-known cognitive bias, the "outcome orientation", to medical questions and describe the harm that the outcome orientation can…

Physics Education · Physics 2017-02-20 Parris Taylor Humphrey , Joanna Masel

When evaluating the effectiveness of a treatment, policy, or intervention, the desired measure of effectiveness may be expensive to collect, not routinely available, or may take a long time to occur. In these cases, it is sometimes possible…

Methodology · Statistics 2022-11-10 Denis Agniel , Layla Parast , Boris Hejblum

A central challenge in Human Immunodeficiency Virus (HIV) public health policy lies in determining whether to universally expand treatment access, despite the risk of sub-optimal adherence and consequent drug resistance, or to adopt a more…

Quantitative Methods · Quantitative Biology 2025-07-16 Ashish Poonia , Siddhartha P. Chakrabarty

Data from observational studies (OSs) is widely available and readily obtainable yet frequently contains confounding biases. On the other hand, data derived from randomized controlled trials (RCTs) helps to reduce these biases; however, it…

Methodology · Statistics 2024-10-30 Dong Yao , Caizhi Tang , Qing Cui , Longfei Li

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

During drug development, evidence can emerge to suggest a treatment is more effective in a specific patient subgroup. Whilst early trials may be conducted in biomarker-mixed populations, later trials are more likely to enrol…

Methodology · Statistics 2023-06-07 Lorna Wheaton , Dan Jackson , Sylwia Bujkiewicz

Using administrative patient-care data such as Electronic Health Records (EHR) and medical/ pharmaceutical claims for population-based scientific research has become increasingly common. With vast sample sizes leading to very small standard…

Methodology · Statistics 2023-08-21 Ritoban Kundu , Xu Shi , Jean Morrison , Jessica Barrett , Bhramar Mukherjee

Active-controlled trials with non-inferiority objectives are often used when effective interventions are available, but new options may offer advantages or meet public health needs. In these trials, participants are randomized to an…

Methodology · Statistics 2025-10-28 Antonio Olivas-Martinez , Fei Gao , Holly Janes

Background: Cancer drugs receive licensing extensions to include additional indications as trial evidence on treatment effectiveness accumulates. We investigate how sharing information across indications can strengthen the inferences…

Practitioners often use data from a randomized controlled trial to learn a treatment assignment policy that can be deployed on a target population. A recurring concern in doing so is that, even if the randomized trial was well-executed…

Econometrics · Economics 2023-04-25 Lihua Lei , Roshni Sahoo , Stefan Wager

Surrogate markers are often used in clinical trials to evaluate treatment effects when primary outcomes are costly, invasive, or take a long time to observe. However, reliance on surrogates can lead to the surrogate paradox, where a…

Methodology · Statistics 2025-06-17 Emily Hsiao , Lu Tian , Layla Parast

Model selection aims to identify a sufficiently well performing model that is possibly simpler than the most complex model among a pool of candidates. However, the decision-making process itself can inadvertently introduce non-negligible…

Methodology · Statistics 2024-08-08 Yann McLatchie , Aki Vehtari

In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment…

Methodology · Statistics 2022-10-05 Dasom Lee , Shu Yang , Xiaofei Wang