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In the quest for enhanced HIV prevention methods, the advent of antiretroviral drugs as pre-exposure prophylaxis (PrEP) has marked a significant stride forward. However, the ethical challenges in conducting placebo-controlled trials for new…

Methodology · Statistics 2024-07-09 Fei Gao , Holly Janes , Susan Buchbinder , Deborah Donnell

Difference-in-differences is a popular method for observational health policy evaluation. It relies on a causal assumption that in the absence of intervention, treatment groups' outcomes would have evolved in parallel to those of comparison…

Methodology · Statistics 2026-02-09 Alyssa Bilinski , Laura A. Hatfield

Three-arm `gold-standard' non-inferiority trials are recommended for indications where only unstable reference treatments are available and the use of a placebo group can be justified ethically. For such trials several study designs have…

Methodology · Statistics 2025-03-20 Martin Scharpenberg , Werner Brannath

The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient…

Methodology · Statistics 2024-10-29 Thomas Burnett , Thomas Jaki

A common concern in non-inferiority (NI) trials is that non adherence due, for example, to poor study conduct can make treatment arms artificially similar. Because intention to treat analyses can be anti-conservative in this situation, per…

Methodology · Statistics 2023-12-04 Katy E Morgan , Ian R White , Clémence Leyrat , Simon Stanworth , Brennan C Kahan

Though platform trials have been touted for their flexibility and streamlined use of trial resources, their statistical efficiency is not well understood. We fill this gap by establishing their greater efficiency for comparing the relative…

Methodology · Statistics 2022-01-28 Tzu-Jung Huang , Alex Luedtke , the AMP Investigators Group

For indications where only unstable reference treatments are available and use of placebo is ethically justified, three-arm `gold standard' designs with an experimental, reference and placebo arm are recommended for non-inferiority trials.…

Methodology · Statistics 2022-10-18 Werner Brannath , Martin Scharpenberg , Sylvia Schmidt

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,…

Cross-sectional incidence estimation based on recency testing has become a widely used tool in HIV research. Recently, this method has gained prominence in HIV prevention trials to estimate the "placebo" incidence that participants might…

Methodology · Statistics 2024-12-18 Jianan Pan , Marlena Bannick , Fei Gao

In many clinical settings, an active-controlled trial design (e.g., a non-inferiority or superiority design) is often used to compare an experimental medicine to an active control (e.g., an FDA-approved, standard therapy). One prominent…

Methodology · Statistics 2024-01-01 Qijia He , Fei Gao , Oliver Dukes , Sinead Delany-Moretlwe , Bo Zhang

Platform trials gained popularity during the last few years as they increase flexibility compared to multi-arm trials by allowing new experimental arms entering when the trial already started. Using a shared control group in platform trials…

We propose a multi-metric flexible Bayesian framework to support efficient interim decision-making in multi-arm multi-stage phase II clinical trials. Multi-arm multi-stage phase II studies increase the efficiency of drug development, but…

Applications · Statistics 2023-12-15 Suzanne M. Dufault , Angela M. Crook , Katie Rolfe , Patrick P. J. Phillips

Simultaneous tests of superiority and non-inferiority hypotheses on multiple endpoints are often performed in clinical trials to demonstrate that a new treatment is superior over a control on at least one endpoint and non-inferior on the…

Methodology · Statistics 2023-10-02 Wenfeng Chen , Naiqing Zhao , Guoyou Qin , Jie Chen

Recent work has focused on nonparametric estimation of conditional treatment effects, but inference has remained relatively unexplored. We propose a class of nonparametric tests for both quantitative and qualitative treatment effect…

Methodology · Statistics 2026-04-07 Oliver Dukes , Mats J. Stensrud , Riccardo Brioschi , Aaron Hudson

With the advent of effective pre-exposure prophylaxis agents, active-controlled HIV prevention trials have become a common study design. Nevertheless, estimating absolute efficacy relative to a placebo remains important. In this paper, we…

Background. Non-inferiority (NI) trials are increasingly used to evaluate new treatments expected to have secondary advantages over standard of care, but similar efficacy on the primary outcome. When designing a NI trial with a binary…

Artificial intelligence (AI) holds great promise for supporting clinical trials, from patient recruitment and endpoint assessment to treatment response prediction. However, deploying AI without safeguards poses significant risks,…

Machine Learning · Computer Science 2025-10-09 Yao Chen , David Ohlssen , Aimee Readie , Gregory Ligozio , Ruvie Martin , Thibaud Coroller

The goal of a well-controlled study is to remove unwanted variation when estimating the causal effect of the intervention of interest. Experiments conducted in the basic sciences frequently achieve this goal using experimental controls,…

Methodology · Statistics 2021-04-22 Kristen B. Hunter , Kristen Koenig , Marie-Abèle Bind

It is generally believed that bias is minimized in well-controlled randomized clinical trials. However, bias can arise in active controlled noninferiority trials because the inference relies on a previously estimated effect size obtained…

Applications · Statistics 2013-12-02 Lei Nie , Zhiwei Zhang , Daniel Rubin , Jianxiong Chu

Background: Advanced adaptive randomised clinical trials are increasingly used. Compared to their conventional counterparts, their flexibility may make them more efficient, increase the probability of obtaining conclusive results without…

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