EconPapers    
Economics at your fingertips  
 

Flexible use of copula‐type model for dose‐finding in drug combination clinical trials

Koichi Hashizume, Jun Tshuchida and Takashi Sozu

Biometrics, 2022, vol. 78, issue 4, 1651-1661

Abstract: Identification of the maximum tolerated dose combination (MTDC) of cancer drugs is an important objective in phase I oncology trials. Numerous dose‐finding designs for drug combination have been proposed over the years. Copula‐type models exhibit distinctive advantages in this task over other models used in existing competitive designs. For example, their application enables the consideration of dose‐limiting toxicities attributable to one of two agents. However, if a particular combination therapy demonstrates extremely synergistic toxicity, copula‐type models are liable to induce biases in toxicity probability estimators due to the associated Fréchet–Hoeffding bounds. Consequently, the dose‐finding performance may be worse than those of other competitive designs. The objective of this study is to improve the performance of dose‐finding designs based on copula‐type models while maintaining their advantageous properties. We propose an extension of the parameter space of the interaction term in copula‐type models. This releases the Fréchet–Hoeffding bounds, making the estimation of toxicity probabilities more flexible. Numerical examples in various scenarios demonstrate that the performance (e.g., the percentage of correct MTDC selection) of the proposed method is better than those exhibited by existing copula‐type models and comparable with those of other competitive designs, irrespective of the existence of extreme synergistic toxicity. The results obtained in this study could motivate the real‐world application of the proposed method in cases requiring the utilization of the properties of copula‐type models.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://doi.org/10.1111/biom.13510

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:bla:biomet:v:78:y:2022:i:4:p:1651-1661

Ordering information: This journal article can be ordered from
http://www.blackwell ... bs.asp?ref=0006-341X

Access Statistics for this article

More articles in Biometrics from The International Biometric Society
Bibliographic data for series maintained by Wiley Content Delivery ().

 
Page updated 2025-03-19
Handle: RePEc:bla:biomet:v:78:y:2022:i:4:p:1651-1661