Bayesian Uncertainty-Directed Dose Finding Designs

Domenicano, I.; Cellamare, Matteo; Mak, Raymond H.; Trippa, Lorenzo

doi:10.1111/rssc.12355

Cited by 5 publications

(3 citation statements)

References 52 publications

(115 reference statements)

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“…This DDP segment includes a phase I trial using the Continual Reassessment Method (CRM) design [ 26 ] followed by a phase II single-arm trial. This example and the simulation parameters were motivated by a phase I trial in non-small cell lung cancer that we designed at the Dana-Farber Cancer Institute [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…The scenarios that we use to illustrate these simulation models are motivated by our previous work on the design of early stage trials in newly diagnosed glioblastoma [ 19 – 22 ], lung cancer [ 23 ], and breast cancer [ 24 ]. In all three examples, we discuss how the use of flexible simulation models of the DDP can be stylized to the clinical setting, support the design of early-phase trials.…”

Section: Introductionmentioning

confidence: 99%

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Looking ahead in early-phase trial design to improve the drug development process: examples in oncology

Vanderbeek

Redd

Trippa

2023

BMC Med Res Methodol

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Background Clinical trial design must consider the specific resource constraints and overall goals of the drug development process (DDP); for example, in designing a phase I trial to evaluate the safety of a drug and recommend a dose for a subsequent phase II trial. Here, we focus on design considerations that involve the sequence of clinical trials, from early phase I to late phase III, that constitute the DDP. Methods We discuss how stylized simulation models of clinical trials in an oncology DDP can quantify important relationships between early-phase trial designs and their consequences for the remaining phases of development. Simulations for three illustrative settings are presented, using stylized models of the DDP that mimic trial designs and decisions, such as the potential discontinuation of the DDP. Results We describe: (1) the relationship between a phase II single-arm trial sample size and the likelihood of a positive result in a subsequent phase III confirmatory trial; (2) the impact of a phase I dose-finding design on the likelihood that the DDP will produce evidence of a safe and effective therapy; and (3) the impact of a phase II enrichment trial design on the operating characteristics of a subsequent phase III confirmatory trial. Conclusions Stylized models of the DDP can support key decisions, such as the sample size, in the design of early-phase trials. Simulation models can be used to estimate performance metrics of the DDP under realistic scenarios; for example, the duration and the total number of patients enrolled. These estimates complement the evaluation of the operating characteristics of early-phase trial design, such as power or accuracy in selecting safe and effective dose levels.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Looking ahead in early-phase trial design to improve the drug development process: examples in oncology

Vanderbeek

Redd

Trippa

2023

BMC Med Res Methodol

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“…BUDs for dose-finding and basket trials have been discussed in [17] and [31]. Previous work, related to BUDs, proposed information-based sampling schemes [11,28,30].…”

Section: Introductionmentioning

confidence: 99%

Approximating the Operating Characteristics of Bayesian Uncertainty Directed Trial Designs

Bonsaglio¹,

Fortini²,

Trippa³

2021

Preprint

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Bayesian response adaptive clinical trials are currently evaluating experimental therapies for several diseases. Adaptive decisions, such as pre-planned variations of the randomization probabilities, attempt to accelerate the development of new treatments.The design of response adaptive trials, in most cases, requires time consuming simulation studies to describe operating characteristics, such as type I/II error rates, across plausible scenarios. We investigate large sample approximations of pivotal operating characteristics in Bayesian Uncertainty directed trial Designs (BUDs). A BUD trial utilizes an explicit metric u to quantify the information accrued during the study on parameters of interest, for example the treatment effects. The randomization probabilities vary during time to minimize the uncertainty summary u at completion of the study.We provide an asymptotic analysis (i) of the allocation of patients to treatment arms and (ii) of the randomization probabilities. For BUDs with outcome distributions belonging to the natural exponential family with quadratic variance function, we illustrate the asymptotic normality of the number of patients assigned to each arm and

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Approximating the operating characteristics of Bayesian Uncertainty directed trial Designs

Bonsaglio

Fortini

Trippa

2022

Journal of Statistical Planning and Inference

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Bayesian Uncertainty-Directed Dose Finding Designs

Cited by 5 publications

References 52 publications

Looking ahead in early-phase trial design to improve the drug development process: examples in oncology

Looking ahead in early-phase trial design to improve the drug development process: examples in oncology

Approximating the Operating Characteristics of Bayesian Uncertainty Directed Trial Designs

Approximating the operating characteristics of Bayesian Uncertainty directed trial Designs

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