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The primary goal of a two-stage Phase I/II trial is to identify the optimal dose for the following large-scale Phase III trial. Recently, Phase I dose-finding designs have shifted from identifying the maximum tolerated dose (MTD) to the…

Methodology · Statistics 2025-01-16 Hao Sun , Jerry Li

Approximate Bayesian Computation is widely used to infer the parameters of discrete-state continuous-time Markov networks. In this work, we focus on models that are governed by the Chemical Master Equation (the CME). Whilst originally…

Quantitative Methods · Quantitative Biology 2020-01-10 Christopher Lester

Approximate Bayesian Computation (ABC) methods are increasingly used for inference in situations in which the likelihood function is either computationally costly or intractable to evaluate. Extensions of the basic ABC rejection algorithm…

Computation · Statistics 2020-05-01 Umberto Simola , Jessica Cisewski-Kehe , Michael U. Gutmann , Jukka Corander

Approximate Bayesian computation (ABC) is a popular likelihood-free inference method for models with intractable likelihood functions. As ABC methods usually rely on comparing summary statistics of observed and simulated data, the choice of…

Machine Learning · Statistics 2022-06-22 Ayush Bharti , Louis Filstroff , Samuel Kaski

Models defined by stochastic differential equations (SDEs) allow for the representation of random variability in dynamical systems. The relevance of this class of models is growing in many applied research areas and is already a standard…

Methodology · Statistics 2014-08-06 Umberto Picchini

Approximate Bayesian computation (ABC) is now an established technique for statistical inference used in cases where the likelihood function is computationally expensive or not available. It relies on the use of a~model that is specified in…

Computation · Statistics 2020-06-02 Richard G. Everitt , Paulina A. Rowińska

Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing…

Computation · Statistics 2025-03-11 Michael Sweeting , Daniel Slade , Dan Jackson , Kristian Brock

Approximate Bayesian computation (ABC) is a method for Bayesian inference when the likelihood is unavailable but simulating from the model is possible. However, many ABC algorithms require a large number of simulations, which can be costly.…

Machine Learning · Statistics 2018-10-15 Marko Järvenpää , Michael U. Gutmann , Arijus Pleska , Aki Vehtari , Pekka Marttinen

A general framework is proposed for Bayesian model-based designs of Phase I cancer trials, in which a general criterion for coherence (Cheung, 2005) of a design is also developed. This framework can incorporate both "individual" and…

Methodology · Statistics 2011-08-08 Jay Bartroff , Tze Leung Lai

In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…

Methodology · Statistics 2026-05-07 Yuxuan Chen , Haiming Zhou , Keiko Nakajima , Philip He

In parametric Bayesian designs of early phase cancer clinical trials with drug combinations exploring a discrete set of partially ordered doses, several authors claimed that there is no added value in including an interaction term to model…

Methodology · Statistics 2022-08-12 Mourad Tighiouart , José L. Jiménez , Marcio A. Diniz , André Rogatko

The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…

Methodology · Statistics 2023-08-31 Peng Yang , Daniel Li , Ruitao Lin , Bo Huang , Ying Yuan

Monte Carlo (MC) simulations provide gold-standard accuracy for carbon ion therapy dose calculations but are computationally intensive. Analytical pencil beam algorithms offer speed but reduced accuracy in heterogeneous tissues. We…

Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly non-monotonic dose-response…

Methodology · Statistics 2024-02-13 James Willard , Shirin Golchi , Erica E. M. Moodie , Bruno Boulanger , Bradley P. Carlin

Approximate Bayesian computation (ABC) is an approach for sampling from an approximate posterior distribution in the presence of a computationally intractable likelihood function. A common implementation is based on simulating model,…

Methodology · Statistics 2013-01-16 D. Prangle , M. G. B. Blum , G. Popovic , S. A. Sisson

Phase I dose-finding studies aim at identifying the maximal tolerated dose (MTD). It is not uncommon that several dose-finding studies are conducted, although often with some variation in the administration mode or dose panel. For instance,…

Quantitative Methods · Quantitative Biology 2021-03-24 Moreno Ursino , Christian Röver , Sarah Zohar , Tim Friede

Approximate Bayesian computation (ABC) or likelihood-free inference algorithms are used to find approximations to posterior distributions without making explicit use of the likelihood function, depending instead on simulation of sample data…

Computation · Statistics 2015-09-08 Richard D. Wilkinson

Phase I dose-escalation trials must be guided by a safety model in order to avoid exposing patients to unacceptably high risk of toxicities. Traditionally, these trials are based on one type of schedule. In more recent practice, however,…

Methodology · Statistics 2020-08-18 Burak Kürsad Günhan , Sebastian Weber , Tim Friede

The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the best balance between benefit and risk, rather…

Methodology · Statistics 2023-09-13 Ying Yuan , Heng Zhou , Suyu Liu

We examine nonparametric dose-finding designs that use toxicity estimates based on all available data at each dose allocation decision. We prove that one such design family, called here "interval design", converges almost surely to the…

Methodology · Statistics 2012-02-22 Assaf P. Oron , David Azriel , Peter D. Hoff