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An accurate estimation of the dose-response relationship is important to determine the optimal dose. For this purpose, a dose finding trial in which subjects are randomized to a few fixed dose levels is the most commonly used design. Often,…

Methodology · Statistics 2025-08-07 Jixian Wang , Zhiwei Zhang , Ram Tiwari

Aims: Combinations of treatments can offer additional benefit over the treatments individually. However, trials of these combinations are lower priority than the development of novel therapies, which can restrict funding, timelines and…

This paper constructs a doubly robust estimator for continuous dose-response estimation. An outcome regression model is augmented with a set of inverse generalized propensity score covariates to correct for potential misspecification bias.…

Statistics Theory · Mathematics 2015-06-17 Daniel J. Graham , Emma J. McCoy , David A. Stephens

In empirical studies with time-to-event outcomes, investigators often leverage observational data to conduct causal inference on the effect of exposure when randomized controlled trial data is unavailable. Model misspecification and lack of…

Methodology · Statistics 2023-05-05 Shenbo Xu , Bang Zheng , Bowen Su , Stan Finkelstein , Roy Welsch , Kenney Ng , Ioanna Tzoulaki , Zach Shahn

Consider sensitivity analysis for estimating average treatment effects under unmeasured confounding, assumed to satisfy a marginal sensitivity model. At the population level, we provide new representations for the sharp population bounds…

Methodology · Statistics 2022-09-26 Zhiqiang Tan

Successful pharmaceutical drug development requires finding correct doses that provide an optimum balance between efficacy and toxicity. Competing responses to dose such as efficacy and toxicity often will increase with dose, and it is…

Applications · Statistics 2024-01-26 A. Lawrence Gould

In placebo-controlled randomized trials, the post-randomization use of concomitant medications may be higher in the placebo arm than in the treatment arm. This may dilute the full benefits of the randomized drug as estimated by the…

Practitioners in medicine, business, political science, and other fields are increasingly aware that decisions should be personalized to each patient, customer, or voter. A given treatment (e.g. a drug or advertisement) should be…

Machine Learning · Statistics 2018-06-15 Alejandro Schuler , Michael Baiocchi , Robert Tibshirani , Nigam Shah

Randomized Controlled Trials (RCT) are the current gold standards to empirically measure the effect of a new drug. However, they may be of limited size and resorting to complementary non-randomized data, referred to as observational, is…

Methodology · Statistics 2025-06-11 Ahmed Boughdiri , Julie Josse , Erwan Scornet

Mixed Models for Repeated Measures (MMRMs) are ubiquitous when analyzing outcomes of clinical trials. However, the linearity of the fixed-effect structure in these models largely restrict their use to estimating treatment effects that are…

Methodology · Statistics 2023-01-23 Lars Lau Raket

Covariate-specific treatment effects (CSTEs) represent heterogeneous treatment effects across subpopulations defined by certain selected covariates. In this article, we consider marginal structural models where CSTEs are linearly…

Methodology · Statistics 2021-05-25 Peng Wu , Zhiqiang Tan , Wenjie Hu , Xiao-Hua Zhou

We propose a method to reduce variance in treatment effect estimates in the setting of high-dimensional data. In particular, we introduce an approach for learning a metric to be used in matching treatment and control groups. The metric…

Applications · Statistics 2017-12-15 Jonathan Bates , Alexander Cloninger

This paper proposes a novel criterion for the allocation of patients in Phase~I dose-escalation clinical trials aiming to find the maximum tolerated dose (MTD). Conventionally, using a model-based approach the next patient is allocated to…

Methodology · Statistics 2018-07-17 Pavel Mozgunov , Thomas Jaki

Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider…

Methodology · Statistics 2022-09-13 Christian Röver , Moreno Ursino , Tim Friede , Sarah Zohar

In the standard setting of one-way ANOVA with normal errors, a new algorithm, called the Step Down Maximum Mean Selection Algorithm (SDMMSA), is proposed to estimate the treatment means under an assumption that the treatment mean is…

Statistics Theory · Mathematics 2008-01-03 Weizhen Wang , Jianan Peng

We propose a new estimator for average causal effects of a binary treatment with panel data in settings with general treatment patterns. Our approach augments the popular two-way-fixed-effects specification with unit-specific weights that…

Econometrics · Economics 2024-03-06 Dmitry Arkhangelsky , Guido W. Imbens , Lihua Lei , Xiaoman Luo

Statistical methodology for the design and analysis of clinical Phase II dose response studies, with related software implementation, are well developed for the case of a normally distributed, homoscedastic response considered for a single…

Methodology · Statistics 2014-05-09 José Pinheiro , Björn Bornkamp , Ekkehard Glimm , Frank Bretz

Marginal structural models are a popular tool for investigating the effects of time-varying treatments, but they require an assumption of no unobserved confounders between the treatment and outcome. With observational data, this assumption…

Methodology · Statistics 2021-06-10 Matthew Blackwell , Soichiro Yamauchi

Estimating what would be an individual's potential response to varying levels of exposure to a treatment is of high practical relevance for several important fields, such as healthcare, economics and public policy. However, existing methods…

Machine Learning · Computer Science 2020-12-11 Patrick Schwab , Lorenz Linhardt , Stefan Bauer , Joachim M. Buhmann , Walter Karlen

In randomized dose-finding trials, although drug exposure data form a part of key information for dose selection, the evaluation of the dose-response (DR) relationship often mainly uses DR data. We examine the benefit of…

Methodology · Statistics 2025-08-07 Jixian Wang , Zhiwei Zhang , Ram Tiwari