Random-effects meta-analysis of phase I dose-finding studies using stochastic process priors

DOI10.1214/20-AOAS1390zbMATH Open1475.62269arXiv1908.06733OpenAlexW2967965553MaRDI QIDQ2233150FDOQ2233150

Authors: Moreno Ursino, Sarah Zohar, Tim Friede, Christian Röver 

Publication date: 14 October 2021

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: 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, sorafenib (BAY 43-900) was used as monotherapy in at least 29 phase I trials according to a recent search in clinicaltrials.gov. Since the toxicity may not be directly related to the specific indication, synthesizing the information from several studies might be worthwhile. However, this is rarely done in practice and only a fixed-effect meta-analysis framework was proposed to date. We developed a Bayesian random-effects meta-analysis methodology to pool several phase I trials and suggest the MTD. A curve free hierarchical model on the logistic scale with random effects, accounting for between-trial heterogeneity, is used to model the probability of toxicity across the investigated doses. An Ornstein-Uhlenbeck Gaussian process is adopted for the random effects structure. Prior distributions for the curve free model are based on a latent Gamma process. An extensive simulation study showed good performance of the proposed method also under model deviations. Sharing information between phase I studies can improve the precision of MTD selection, at least when the number of trials is reasonably large.

Full work available at URL: https://arxiv.org/abs/1908.06733

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zbMATH Keywords

meta-analysismixed-effect modeldose finding

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Gaussian processes (60G15) Estimation in multivariate analysis (62H12)

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Cited In (6)

• Bayesian aggregation of average data: an application in drug development
• REDOMA: Bayesian random-effects dose-optimization meta-analysis using spike-and-slab priors
• Dose-finding methods for phase I clinical trials using pharmacokinetics in small populations
• A straightforward meta-analysis approach for oncology phase I dose-finding studies
• MADF
• Bayesian hierarchical random-effects meta-analysis and design of phase I clinical trials

Uses Software

• BayesDA
• dfcrm
• GitHub

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