Continual reassessment method with regularization in phase I clinical trials.

TitleContinual reassessment method with regularization in phase I clinical trials.
Publication TypeJournal Article
Year of Publication2020
AuthorsLi, Xiang, Anastasia Ivanova, Hong Tian, Pilar Lim, and Kevin Liu
JournalJ Biopharm Stat
Date Published2020 Nov 01
KeywordsClinical Trials, Phase I as Topic, Computer Simulation, Dose-Response Relationship, Drug, Humans, Maximum Tolerated Dose, Probability, Research Design

Many Phase I trial designs have been developed to improve upon the standard design. These designs can be classified as long-memory designs, for example, the continual reassessment method (CRM), and short-memory designs such as the modified toxicity probability interval (mTPI) design. Long-term memory designs use all data but their performance can be negatively affected by the model misspecification. Short-term memory designs only use data at the current dose and might lose efficiency as a result. To overcome these issues, we propose a regularized CRM (rCRM). The rCRM offers a trade-off between long-term memory and short-term memory methods. The rCRM gives more weight to data obtained at the doses with the estimated probability of toxicity closer to the target toxicity rate. The addition of a regularization term has an effect of shrinking the dimension of the model and leads to improved performance of the 2-parameter CRM. The rCRM is a good design choice to guide assignments in an expansion cohort phase of a dose-finding trial since dose assignments do not seem to change as often as in corresponding CRMs.

Alternate JournalJ Biopharm Stat
Original PublicationContinual reassessment method with regularization in phase I clinical trials.
PubMed ID32926652
PubMed Central IDPMC7954799
Grant ListP01 CA142538 / CA / NCI NIH HHS / United States