ArticleBiostatistics (Oxford, England)2019
Dose-finding designs for cumulative toxicities using multiple constraints.
Article in Biostatistics (Oxford, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Real-life effectiveness of FLOT in resectable gastric cancer: existing challenges.Drugs in context · 2025Article
- Dose optimization for cancer treatments with considerations for late-onset toxicities.Clinical trials (London, England) · 2024Article
- A Road Map for Designing Phase I Clinical Trials of Radiotherapy-Novel Agent Combinations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
- Bayesian modeling of a bivariate toxicity outcome for early phase oncology trials evaluating dose regimens.Statistics in medicine · 2021Article
- Seamless phase I/II design for novel anticancer agents with competing disease progression.Statistics in medicine · 2021Article
- Designing Dose-Finding Phase I Clinical Trials: Top 10 Questions That Should Be Discussed With Your Statistician.JCO precision oncology · 2021Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
This article addresses the concern regarding late-onset dose-limiting toxicities (DLT), moderate toxicities below the threshold of a DLT and cumulative toxicities that may lead to a DLT, which are mostly disregarded or handled in an ad hoc manner when determining the maximum tolerated dose (MTD) in dose-finding cancer clinical trials. An extension of the Time-to-Event Continual Reassessment Method (TITE-CRM) which allows for the specification of toxicity constraints on both DLT and moderate toxicities, and can account for partial information is proposed. The method is illustrated in the context of an Erlotinib dose-finding trial with low DLT rates, but a significant number of moderate toxicities leading to treatment discontinuation in later cycles. Based on simulations, our method performs well at selecting the dose level that satisfies both the DLT and moderate-toxicity constraints. Moreover, it has similar probability of correct selection compared to the TITE-CRM when the true MTD based on DLT only and the true MTD based on grade 2 or higher toxicities alone coincide, but reduces the probability of recommending a dose above the MTD.
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Registered trials
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