ArticleBMC medical research methodology2024
Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial.
Article in BMC medical research methodology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
2 citing papers in PubMed, 1 synthesis or guideline pooled it, 2 citations in OpenAlex.
- Prevalence and characteristics of persistent pain among head and neck cancer survivors: a systematic review and meta-analysis.Pain medicine (Malden, Mass.) · 2025Pooled it
- Design of a Phase I Drug Combination Study with Adaptive Allocation Based on Dose-Limiting Toxicity Attribution.Cancers · 2025Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIn this article we describe the methodology of the time-to-event continual reassessment method in the presence of partial orders (PO-TITE-CRM) and the process of implementing this trial design into a phase I trial in head and neck cancer called ADePT-DDR. The ADePT-DDR trial aims to find the maximum tolerated dose of an ATR inhibitor given in conjunction with radiotherapy in patients with head and neck squamous cell carcinoma.
methodsThe PO-TITE-CRM is a phase I trial design that builds upon the time-to-event continual reassessment method (TITE-CRM) to allow for the presence of partial ordering of doses. Partial orders occur in the case where the monotonicity assumption does not hold and the ordering of doses in terms of toxicity is not fully known.
resultsWe arrived at a parameterisation of the design which performed well over a range of scenarios. Results from simulations were used iteratively to determine the best parameterisation of the design and we present the final set of simulations. We provide details on the methodology as well as insight into how it is applied to the trial.
conclusionsWhilst being a very efficient design we highlight some of the difficulties and challenges that come with implementing such a design. As the issue of partial ordering may become more frequent due to the increasing investigations of combination therapies we believe this account will be beneficial to those wishing to implement a design with partial orders.
trial registrationADePT-DDR was added to the European Clinical Trials Database (EudraCT number: 2020-001034-35) on 2020-08-07.
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Registered trials
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.