Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial
Abstract Background In 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...
| المؤلفون الرئيسيون: | , , , , , , , |
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| التنسيق: | مقال |
| اللغة: | English |
| منشور في: |
BMC
2024-01-01
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| سلاسل: | BMC Medical Research Methodology |
| الموضوعات: | |
| الوصول للمادة أونلاين: | https://doi.org/10.1186/s12874-024-02142-4 |
| _version_ | 1827382125273284608 |
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| author | Amit Patel Kristian Brock Daniel Slade Claire Gaunt Anthony Kong Hisham Mehanna Lucinda Billingham Piers Gaunt |
| author_facet | Amit Patel Kristian Brock Daniel Slade Claire Gaunt Anthony Kong Hisham Mehanna Lucinda Billingham Piers Gaunt |
| author_sort | Amit Patel |
| collection | DOAJ |
| description | Abstract Background In 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. Methods The 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. Results We 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. Conclusions Whilst 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 registration ADePT-DDR was added to the European Clinical Trials Database (EudraCT number: 2020-001034-35) on 2020-08-07. |
| first_indexed | 2024-03-08T14:15:02Z |
| format | Article |
| id | doaj.art-482169edd81b4cb08d5b3a47c93c2213 |
| institution | Directory Open Access Journal |
| issn | 1471-2288 |
| language | English |
| last_indexed | 2024-03-08T14:15:02Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Research Methodology |
| spelling | doaj.art-482169edd81b4cb08d5b3a47c93c22132024-01-14T12:27:40ZengBMCBMC Medical Research Methodology1471-22882024-01-0124111210.1186/s12874-024-02142-4Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trialAmit Patel0Kristian Brock1Daniel Slade2Claire Gaunt3Anthony Kong4Hisham Mehanna5Lucinda Billingham6Piers Gaunt7Cancer Research Clinical Trials Unit, University of BirminghamCancer Research Clinical Trials Unit, University of BirminghamCancer Research Clinical Trials Unit, University of BirminghamCancer Research Clinical Trials Unit, University of BirminghamDepartment of Oncology, King’s College LondonCancer Research Clinical Trials Unit, University of BirminghamCancer Research Clinical Trials Unit, University of BirminghamCancer Research Clinical Trials Unit, University of BirminghamAbstract Background In 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. Methods The 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. Results We 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. Conclusions Whilst 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 registration ADePT-DDR was added to the European Clinical Trials Database (EudraCT number: 2020-001034-35) on 2020-08-07.https://doi.org/10.1186/s12874-024-02142-4PO-TITE-CRMADePT-DDRToxicityDose-findingPartial ordersMonotonicity assumption |
| spellingShingle | Amit Patel Kristian Brock Daniel Slade Claire Gaunt Anthony Kong Hisham Mehanna Lucinda Billingham Piers Gaunt Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial BMC Medical Research Methodology PO-TITE-CRM ADePT-DDR Toxicity Dose-finding Partial orders Monotonicity assumption |
| title | Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial |
| title_full | Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial |
| title_fullStr | Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial |
| title_full_unstemmed | Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial |
| title_short | Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial |
| title_sort | implementing the time to event continual reassessment method in the presence of partial orders in a phase i head and neck cancer trial |
| topic | PO-TITE-CRM ADePT-DDR Toxicity Dose-finding Partial orders Monotonicity assumption |
| url | https://doi.org/10.1186/s12874-024-02142-4 |
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