Trial reportBMC medical research methodology2017
Implementing the EffTox dose-finding design in the Matchpoint trial.
Trial report in BMC medical research methodology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Generalized Pairwise Comparisons in Dose Optimization Oncology Trials: Beyond Safety to Multi-outcome Dose Selection.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- DOSET: dose optimization with simultaneous efficacy and toxicity evaluation, motivated by a first-in-human phase I CAR T lymphoma trial.ESMO open · 2026Article
- 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
- Defining Utility as a Measure of Preference Under Uncertainty in Phase I-II Oncology Dose Finding Trials.Statistics in medicine · 2026Article
- Clinical Trial Simulation: Planning With the OCTAVE Framework, Implementation and Validation Principles.Statistics in medicine · 2026Article
- Using circulating tumor DNA as a novel biomarker of efficacy for dose-finding designs in oncology.Statistical methods in medical research · 2025Article
- SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.EClinicalMedicine · 2025Article
- Accelerated-phase CML: de novo and transformed.Hematology. American Society of Hematology. Education Program · 2023Article
- Early phase clinical trials in oncology: Realising the potential of seamless designs.European journal of cancer (Oxford, England : 1990) · 2023Article
- Practical implementation of the partial ordering continual reassessment method in a Phase I combination-schedule dose-finding trial.Statistics in medicine · 2022Article
- The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design.Vaccines · 2022Article
- Mathematical Modelling for Optimal Vaccine Dose Finding: Maximising Efficacy and Minimising Toxicity.Vaccines · 2022Article
- Practical recommendations for implementing a Bayesian adaptive phase I design during a pandemic.BMC medical research methodology · 2022Article
- Operating characteristics are needed to properly evaluate the scientific validity of phase I protocols.Contemporary clinical trials · 2021Article
- Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer.BMC cancer · 2021Article
- Using an Interaction Parameter in Model-Based Phase I Trials for Combination Treatments? A Simulation Study.International journal of environmental research and public health · 2021Article
- A Bayesian phase 2 model based adaptive design to optimise antivenom dosing: Application to a dose-finding trial for a novel Russell's viper antivenom in Myanmar.PLoS neglected tropical diseases · 2020Article
- A curve free Bayesian decision-theoretic design for phase Ia/Ib trials considering both safety and efficacy outcomes.Statistics in biosciences · 2020Article
- How to design a dose-finding study using the continual reassessment method.BMC medical research methodology · 2019Article
- Adaptive designs in clinical trials: why use them, and how to run and report them.BMC medicine · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe Matchpoint trial aims to identify the optimal dose of ponatinib to give with conventional chemotherapy consisting of fludarabine, cytarabine and idarubicin to chronic myeloid leukaemia patients in blastic transformation phase. The dose should be both tolerable and efficacious. This paper describes our experience implementing EffTox in the Matchpoint trial.
methodsEffTox is a Bayesian adaptive dose-finding trial design that jointly scrutinises binary efficacy and toxicity outcomes. We describe a nomenclature for succinctly describing outcomes in phase I/II dose-finding trials. We use dose-transition pathways, where doses are calculated for each feasible set of outcomes in future cohorts. We introduce the phenomenon of dose ambivalence, where EffTox can recommend different doses after observing the same outcomes. We also describe our experiences with outcome ambiguity, where the categorical evaluation of some primary outcomes is temporarily delayed.
resultsWe arrived at an EffTox parameterisation that is simulated to perform well over a range of scenarios. In scenarios where dose ambivalence manifested, we were guided by the dose-transition pathways. This technique facilitates planning, and also helped us overcome short-term outcome ambiguity.
conclusionsEffTox is an efficient and powerful design, but not without its challenges. Joint phase I/II clinical trial designs will likely become increasingly important in coming years as we further investigate non-cytotoxic treatments and streamline the drug approval process. We hope this account of the problems we faced and the solutions we used will help others implement this dose-finding clinical trial design.
trial registrationMatchpoint was added to the European Clinical Trials Database ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005629-65/GB ) on 2013-12-30.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.