Isotonic Design for Phase I Clinical Trials: Can We Improve Further?
Isotonic design for phase I clinical trials
One of the most challenging tasks in clinical trials is finding the maximum tolerated dose (MTD) to be tested in the next phase. An assurance for the safety of the patients and recommendation of a suitable dose for phase II are the main objectives of a phase I trial. The MTD can be identified through various approaches. A non-parametric approach, known as the isotonic design, has been explored in our study. The design relies on the monotonicity assumption of the dose-toxicity relationship. Usually the number of patients in a trial have an impact on the adequacy of dose recommendation. This paper is a humble attempt to see the impact of cohort size and total cohorts on the isotonic design. It investigates the possibility of improving the current algorithm of the isotonic design for escalation and de-escalation. Also, the paper proposes a stopping rule to avoid any severely toxic dose as the MTD. The simulation study shows that along with total cohort, cohort size also has an appreciable effect on the MTD selection. The proposed modification of the algorithm has also been found to work satisfactorily in majority of the cases.
How to Cite
Copyright (c) 2019 Austrian Journal of Statistics
This work is licensed under a Creative Commons Attribution 3.0 International License.
The Austrian Journal of Statistics publish open access articles under the terms of the Creative Commons Attribution (CC BY) License.
The Creative Commons Attribution License (CC-BY) allows users to copy, distribute and transmit an article, adapt the article and make commercial use of the article. The CC BY license permits commercial and non-commercial re-use of an open access article, as long as the author is properly attributed.
Copyright on any research article published by the Austrian Journal of Statistics is retained by the author(s). Authors grant the Austrian Journal of Statistics a license to publish the article and identify itself as the original publisher. Authors also grant any third party the right to use the article freely as long as its original authors, citation details and publisher are identified.
Manuscripts should be unpublished and not be under consideration for publication elsewhere. By submitting an article, the author(s) certify that the article is their original work, that they have the right to submit the article for publication, and that they can grant the above license.