ArticleStatistics in medicine2013
Dose-finding designs using a novel quasi-continuous endpoint for multiple toxicities.
Article in Statistics in medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- PRO-ADD: Patient-empowered dose-finding trials integrating safety, preliminary efficacy and patient-reported outcomes for optimal dose selection.Statistical methods in medical research · 2026Article
- UNITED: A Unified Transparent and Efficient Phase I/II Trial Design for Dose Optimization Accounting for Ordinal Graded, Continuous and Mixed Toxicity and Efficacy Endpoints.Statistics in medicine · 2025Article
- Isotonic Phase I cancer clinical trial design utilizing patient-reported outcomes.Statistics in biopharmaceutical research · 2025Article
- Statistical and practical considerations in planning and conduct of dose-optimization trials.Clinical trials (London, England) · 2024Review
- MT-Keyboard: A Bayesian Model-assisted Interval Design to Account for Toxicity Grades and Types for Phase I Trials.Statistics in biopharmaceutical research · 2024Article
- Application of the patient-reported outcomes continual reassessment method to a phase I study of radiotherapy in endometrial cancer.The international journal of biostatistics · 2023Article
- An overview of the BOIN design and its current extensions for novel early-phase oncology trials.Contemporary clinical trials communications · 2022Review
- An adaptive gBOIN design with shrinkage boundaries for phase I dose-finding trials.BMC medical research methodology · 2021Article
- Bayesian modeling of a bivariate toxicity outcome for early phase oncology trials evaluating dose regimens.Statistics in medicine · 2021Article
- phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.PloS one · 2021Article
- Designing Dose-Finding Phase I Clinical Trials: Top 10 Questions That Should Be Discussed With Your Statistician.JCO precision oncology · 2021Article
- A Bayesian Adaptive Design in Cancer Phase I Trials Using Dose Combinations with Ordinal Toxicity Grades.Stats · 2020Article
- Bayesian Methods in Regulatory Science.Statistics in biopharmaceutical research · 2020Article
- An adaptive multi-stage phase I dose-finding design incorporating continuous efficacy and toxicity data from multiple treatment cycles.Journal of biopharmaceutical statistics · 2019Article
- Dose-finding designs for cumulative toxicities using multiple constraints.Biostatistics (Oxford, England) · 2019Article
- Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.Clinical trials (London, England) · 2018Article
- Repeated measures dose-finding design with time-trend detection in the presence of correlated toxicity data.Clinical trials (London, England) · 2017Article
- A Bayesian dose-finding design incorporating toxicity data from multiple treatment cycles.Statistics in medicine · 2017Article
- Article
- Challenges and Innovations in Phase I Dose-Finding Designs for Molecularly Targeted Agents and Cancer Immunotherapies.Journal of biometrics & biostatistics · 2016Article
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Authors and funding
5 authors.
Funding
Abstract
The aim of a phase I oncology trial is to identify a dose with an acceptable safety profile. Most phase I designs use the dose-limiting toxicity, a binary endpoint, to assess the unacceptable level of toxicity. The dose-limiting toxicity might be incomplete for investigating molecularly targeted therapies as much useful toxicity information is discarded. In this work, we propose a quasi-continuous toxicity score, the total toxicity profile (TTP), to measure quantitatively and comprehensively the overall severity of multiple toxicities. We define the TTP as the Euclidean norm of the weights of toxicities experienced by a patient, where the weights reflect the relative clinical importance of each grade and toxicity type. We propose a dose-finding design, the quasi-likelihood continual reassessment method (CRM), incorporating the TTP score into the CRM, with a logistic model for the dose-toxicity relationship in a frequentist framework. Using simulations, we compared our design with three existing designs for quasi-continuous toxicity score (the Bayesian quasi-CRM with an empiric model and two nonparametric designs), all using the TTP score, under eight different scenarios. All designs using the TTP score to identify the recommended dose had good performance characteristics for most scenarios, with good overdosing control. For a sample size of 36, the percentage of correct selection for the quasi-likelihood CRM ranged from 80% to 90%, with similar results for the quasi-CRM design. These designs with TTP score present an appealing alternative to the conventional dose-finding designs, especially in the context of molecularly targeted agents.
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